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Endocrine system

The document discusses the endocrine system and its components. It describes the different types of regulatory molecules involved in endocrine signaling, including hormones, paracrine factors, and neurotransmitters. It outlines the major endocrine glands and hormones, including the pituitary gland, thyroid gland, parathyroid gland, adrenal glands, pancreas, gonads, and placenta. It explains how hormones can either enter cells and directly influence gene expression or act through second messenger systems by binding to cell surface receptors. The roles of the hypothalamus and pituitary gland in regulating other endocrine organs are also summarized.

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1 The Endocrine System
2 Outline • Types of Regulatory Molecules • Endocrine Glands and Hormones • Paracrine Regulation • Hormones That Enter Cells • Hormones That Do Not Enter Cells • Posterior and Anterior Pituitary Gland • Thyroid and Parathyroid Glands • Adrenal Glands • Other Endocrine Glands
3 SIGNALING AGENTS & FACTORS Neurotransmitters Peptides Oxygen-based molecules, e.g., NO Prostanoids Hormones Cytokines ( some are Chemokines) Extracellular-matrix molecules Nutrients & metabolites Mechanical stimuli, e.g., fluid shear Cell-surface glycoproteins Hormones from endocrine cells & organs are part of a much larger picture of the outside controls on cells Heat, osmolarity, exogenous chemicals, etc ENDOCRINE
4 Types of Regulatory Molecules • Hormone – A regulatory chemical secreted into the blood by an endocrine gland, or an organ exhibiting endocrine function. • Target Cells respond to hormone – Neurohormone – A chemical messenger secreted by neuron into the blood rather than the synaptic cleft. • Paracrine - regulatory molecules work without being transmitted by the blood – not endocrine • Pheromone - communication messengers
5 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Axon Neurotransmitter Endocrine gland Paracrine regulator Receptor proteins Hormone carried by blood Target cell
6 Endocrine Glands and Hormones • Hormones secreted by the endocrine glands belong to four chemical categories: – Polypeptides - short chains of amino acids less than 100 amino acids (insulin & ADH) – Glycoproteins- longer than100 A.A. with carbs (FSH and LH) – Amines - Amines – A.A. derived from tyrosine and tryptophan – epinephrine and norepinephrine and melatonin – Steroids - lipids derived from cholesterol  sex steroids - testosterone, estadiol, progesterone, and cortisol – secreted by testes, ovaries, placenta and adrenal cortex  Corticosteroids - adrenal cortex cortisol and aldosterone (regulates glucose and salt balance) – All hormones can be categorized as lipophilic (fat soluble) or hydrophilic (water soluble).
7 Endocrine Glands and Hormones • Neural and endocrine interactions – Endocrine system also interacts and cooperates with the nervous system to regulate the activities of the other organ systems of the body. – Secretory activity of many endocrine glands controlled by nervous system like  Adrenal medulla, posterior pituitary, and pineal gland  major site for neural regulation is the brain’s regulation of the anterior pituitary by the hypothalmus However many are not under neural control
8 Human Endocrine System major glands
9 cvlAl re u o - - - - - - - diaphragm Parathyroids Adrenal cortex Thyroid Pituitary anterior Pancreas Gonads ENDOCRINE ORGANS I
10 [ non-epithelial origin ] cvlAl re uo - - - - - - - diaphragm Parathyroids Adrenal cortex Thyroid Pituitary anterior Pancreas Gonads ENDOCRINE ORGANS II [Pineal] [Heart] [Adrenal medulla] [Kidney] [Placenta] Plus neuroendocrine cells developed within mature gut, airway, etc epithelia [Pituitary, posterior & Brain] [Adipose tissue]
11 TYPICAL ENDOCRINE GLAND - Context hormone release vessels Clumps of endocrine cells blood control Capillary diffusion TARGET ORGAN Target cells, with receptors for binding 12 transport3 4 5 Target cells’ response 6 Feedback
12 GLAND(S) WHERE CELL TYPES HORMONES SPECIAL Thyroid Neck Follicular cells C cells Thyronine Calcitonin Follicles for storage Parathyroid Neck Chief cells Parathormone /PTH Small Adrenal medulla Over kidney Chromaffin cells Epinephrine Norepinephrine Nerve fibers Adrenal cortex Over kidney Zona glomerulosa Zona fasciculata Zona reticularis Mineralocorticoids Glucocorticoids Sex steroids Pineal Brain’s center Pinealocytes Melatonin Connected for light drive Zones ENDOCRINE ORGANS I
13 GLAND(S) WHERE CELL TYPES HORMONES SPECIAL Pituitary posterior Axons of PV & SO hypothal. neurons Oxytocin Vasopressin /ADH Extension of brain Pancreas Left upper quad Beta, Alpha, Delta, PP cells Insulin Glucagon Somatostatin Pancr Peptide Gonads Pelvic/ Scrotal Granulosa, Theca Lutein, & Leydig Sex steroids Inhibin Placenta Uterus Syncytiotrophoblast Female: for amplified hormonal responses Female: cyclic Pituitary anterior Below brain MTs STs GTs THs CTs Blood drains hypothal.- pituitary for control Prolactin GH LH FSH TSH ACTH Below brain Islets +Pituicytes s ENDOCRINE ORGANS II
14 Paracrine Regulation • Signaling between cells - Local effect and short-lived occurs in many organs • Regulatory molecules – cytokines - regulate different cells of the immune system – growth factors - promote growth and cell division in specific organs – stimulate cell division at target cells
15 Paracrine Regulation • Prostaglandins – most diverse group of paracrine regulators • participate in regulation of: – immune system – inflammation, pain and fever – reproductive system – reproductive function ovulation, labor, – digestive system – inhibit gastric secretions, incrfease motility and fluid absorption – respiratory system - blood vessels constriction and dilation in lungs – circulatory system - blood platelets in blood clotting – urinary system - renal blood flow vasodilation increasing urine excretion • Prostaglandin synthesis inhibited by aspirin. – nonsteroidal anti-inflammatory drug  Ibuprofen  Work to inhibit inflammation and pain by inhibiting enzyme necessary to produce prostaglandins – (cyclooxygenase -2)
16 Hormones That Enter Cells • Lipophilic hormones pass through the target cell’s plasma membrane and bind to intracellular receptor proteins. – hormone receptor complex then binds to specific regions of DNA  activate genes and regulate target cells
17 Steroid Hormone Action
18 Hormones That Do Not Enter Cells • Hormones that are too large or too polar to cross plasma membranes include all of the peptide and glycoprotein hormones, as well as catecholamine hormones epinephrine and norepinephrine. – bind to receptor proteins located on the outer surface of the plasma membrane  cyclic AMP second-messenger system  IP3/CA++ second-messenger system
19 Action of Epinephrine on a Liver Cell 1. Epinephrine is lipophobic and needs to bind to specific receptor proteins on cell surface. 2. Acting through intermediary G proteins the hormone bound receptor activates the enzyme adenenylyl cyclase which converts ATP to cAMP 3. Cyclic AMP performs as a 2ndary messenger and activates protein kinase-A an enzyme that was previously inactive 4. Protein kinase–A phosphorylates and activates the enzyme phosphorylase which catalyses the hydrolysis of glycogen into glucose.
20 IP3/CA++ Second-Messenger System 1. The hormone epinephrine binds to specific receptor proteins on the cell surface. 2. Acting through G- proteins, the hormone-bound receptor activates the enzyme phospholipase C, which converts membrane phospholipids into inositol triphosphate (IP3) 3. IP3 diffuses thru the cytoplasm and binds to receptors on the endoplasmic reticulum 4. The binding of IP3 to the receptor stimulates the endoplasmic reticulum to release Ca++ into the cytoplasm 5. Some of the released Ca++ binds to the receptor protein called calmodulin 6. The Ca++/Calmodulin complex activates other intracellular proteins – producing the horomone effects
21 Primary endocrine organs • Hypothalamus and pituitary gland secrete hormones and regulate other endocrine organs. They are the main regulatory organs of the endocrine system.
22 Hypothalamus • Located below the thalamus and above the pituitary gland (=epiphysis) • Regulates the pituitary gland secretions through two different mechanisms
23 Hypothalamus - neurohypophysis • 1- Neurons, receiving information from receptors, fire APs which travel down to the post pituitary gland and stimulate the release of stored neurohormones – Oxytocin (OT) and anti- diuretic hormone (ADH)
24 Hormones of the posterior pituitary Regulation Hormone Target organ Action Pathology Reflex Oxytocin - Uterus (smooth muscle) - breast tubules (smooth muscles) -labor and delivery - milk-let down -- -- Reflex (osmoreceptor) ADH (vasopressin) - DCT in kidney tubules - promote H2O reabsorption - not enough: diabetes insipidus - too much: ↑ BP?
25 Hypothalamus – adenohypophysis • 2- Upon stimulation, secretory cells located in the hypothalamus secrete “releasing” hormones which travel down a capillary bed toward the anterior pituitary gland (adenopituitary). Each type of releasing hormones will stimulate the secretion and release of a pituitary hormone. • Hormones which control the secretion of other hormones are tropic hormones (found in hypothalamus and pituitary gland
26Figure 6.5 Hormones of the hypothalamus and anterior pituitary gland
27Figure 6.8 Anterior pituitary Regulation Hormone Target organ Action Pathology GHRH and GHIH Growth hormone (GH) Many cells (bones..) Stimulate cell growth and cell division - not enough: children  pituitary dwarfism too much: gigantism (children) – acromegaly (adult) PRH - PIH Prolactin (PL) Breast secretory cells - milk secretion -- TRH Thyroid stimulating hormone (TSH) Thyroid gland - promote thyroid gland secretion (T3 and T4) - not enough: hypothyroidism (cretinism in children) - too much: hyperthyroidism CRH Adrenocorticotropic hormone (ACTH) Adrenal cortex (3 layers) - stimulates secretion of adrenal cortex - not enough: Addison's disease - too much: Cushing syndrome GnRH Gonadotropin - Follicle stimulating hormone (FSH) - Luteinizing hormone (LH) Stimulate gamete maturation Stimulate gonadal gland secretion and gamete formation - infertility
28 Figure 23-17 Same Individual with Acromegaly (evolution over 20 years)
29Figure 6.6 Mechanism of control
30 HYPOPHYSIS/ Pituitary gland Pituitary stalk Posterior lobe Hypoth alamus Anterior lobe Dura IIIrd Ve Intermediatelobe
31 Pars nervosa Infundibular process Pars intermedia PITUITARY SUB-DIVISIONS Hypothalamic SO & PV nuclei Hypothalamic median eminence ADENOHYPOPHYSIS Pars distalis Pars tuberalis NEUROHYPOPHYSIS Infundibular stem neural part of stalk 1 3 2 1 2 3
32 Unlike some other endocrine cells, those of the anterior pituitary separate their supplying a hormone from the detection of the need for the hormone. The sensitivity to need is performed by hypothalamic neurons, which can coordinate requirements for several hormones with drives, and events outside the person. Anterior-pituitary cells & hormones The system also allows for control by inhibitory factors, as well as + driving hormone-releasing factors
33 HYPOTHALAMO-HYPOPHYSEAL Portal flow Superior arteries Portal drainage Hypothalamus Anterior lobe capillaries Dura Hypothalamic capillary bed Neurosecretory neurons Veins 1 2 3 4 5 A portal flow takes venous blood drained from one organ and uses it as a supply to another organ, e.g., gut to liver
34 HYPOTHALAMO-HYPOPHYSEAL Portal flow Superior arteries Portal drainage Hypothalamus Anterior lobe capillaries Hypothalamic capillary bed Neurosecretory neurons Veins 1 2 3 4 5 Portal flow carries factors from hypothalamic neurons to pituitary anterior-lobe cells E.g.,TH-RF from neuron causes Thyrotroph to release TSH
35 Superior arteries Portal drainage Hypothalamus Anterior lobe capillaries Hypothalamic capillary bed Neurosecretory neurons Veins 1 2 3 4 5 Mammotrophs MTs Somatotrophs STs Gonadotrophs GTs Thyrotrophs THs Corticotrophs CTs Blood drains hypothalamus-pituitary for control by RFs, etc Prolactin PRL Growth hormone GH Luteinizing hormone LH Follicle-stimulating hormone FSH Thyroid-stimulating hormone TSH Adrenocorticotrophic hormone ACTH Anterior-pituitary cells & hormones
36 Mammotrophs MTs Somatotrophs STs Gonadotrophs GTs Thyrotrophs THs Corticotrophs CTs Blood drains hypothalamus- pituitary for control by RFs, etc Prolactin PRL Growth hormone GH Luteinizing hormone LH/ICSH Follicle-stimulating hormone FSH Thyroid-stimulating hormone TSH Adrenocorticotrophic hormone ACTH cleaved from pro-opio-melanonocortin/ POMC Anterior-pituitary cells & hormones Acidophil Basophil
37 Anterior-pituitary cells 2 Mammotrophs MTs Somatotrophs STs Gonadotrophs GTs Thyrotrophs THs Corticotrophs CTs Prolactin PRL Growth hormone GH Luteinizing hormone LH FSH TSH ACTH Acidophil Basophil Chromophobe Chromophobes stain weakly, in comparison to CHROMOPHILS - Acidophils & Basophils Folliculo-Stellate cells lie amongst the glandular cells; doing what?
38 Anterior-pituitary cells 3 Corticotrophs CTs ACTH but by selective enzymatic cleavage of a larger 32kDa precursor - pro-opiomelanocortin, also made in the hypothalamus and elsewhere, and there serving to provide other hormones & neurotransmitters Pro-opiomelanocortin ACTH Pro-ACTH β-LPH β-Endorphin β- MSH SP simplified POMC ~ Pro-opiomelanocortin
39 Anterior-pituitary cells 4 Selective enzymatic cleavage of the precursor - pro- opiomelanocortin, provides other hormones & transmitters ACT H β-Endorphin Pro-opiomelanocortinSP NT 1-76 β-LPHACTH β-LPHACTH γ-LPH NT 1-49 JP γ -MSH α-MSH β-MSH elaborate MSH ~ Melanocyte-stimulating hormone NT ~ amino-terminal peptides LPH ~ Lipotropic hormone Pro-hormone convertase 1 Pro-hormone convertase 1 Pro−γ -MSH Pro−γ -MSH After Reudelhuber TL. J Clin Invest 2003;111:1115-1116
40 NEUROHYPOPHYSIS Pars nervosa Hypothalamic SO & PV nuclei Supraoptic & Paraventricular nuclei Hypothalamus 1 2 3 Inferior arteries Veins Release of hormone is separated from production * * * * Neural stalk Optic chiasm
41 NEUROHYPOPHYSIS Pars nervosa Hypothalamic SO & PV nuclei Supraoptic & Paraventricular nuclei Hypothalamus 1 2 3 Inferior arteries Veins * * Neural stalk Optic chiasm Note - the supraoptic nucleus is above the optic nerve & chiasm, but closer to the chiasm is the small suprachiasmatic nucleus (relaying the darkness stimulus indirectly to the pineal gland).
42 NEUROHYPOPHYSIS Pars nervosa axons, terminals, pituicytes & capillaries Hypothalamic SO & PV nucleiHypothalamus Infundibular stem neural part of stalk - axons & glia 1 2 3 Neurosecretory neurons producing oxytocin & vasopressin/ADH Inferior arteries Veins Release of hormone is separated from production * * * *
43 NEUROHYPOPHYSIS Hypothalamic SO & PV nucleiHypothalamus Neurosecretory neurons producing oxytocin & vasopressin/ADH Inferior arteries Veins Hormone travels down the axon bound to the carrier protein - neurophysin, from which it is cleaved for release * *
44 SUCKLING REFLEX Hypothalamic SO & PV neuron activation Hypothalamus * BREAST Myoepithelial-cell contraction Sensory response Oxytocin release Stimulus1 2 3 4 56 7 Milk ejectionVascular transfer
45 PITUITARY Mid-sagittal section of 1-m embryo STOMODEUM PHARYNGEAL ARCHES PITUITARY RATHKE’S POUCH starting in oral ectoderm BRAIN I II
46 PITUITARY DEVELOPMENT II Neural-tube diencephalic ectoderm Oral-pharyngeal lining ectoderm IIIrd Ve Rathke’s pouch Pars tuberalis Pars distalis Pars intermedia Pars nervosa Infundibular stem Hypothalamus ADENOHYPOPHYSIS NEUROHYPOPHYSIS
47 PITUITARY DEVELOPMENT II Pars tuberalis Pars distalis Pars intermedia Pars nervosa Infundibular stem Hypothalamus Pars nervosa Infundibular process Pars intermedia Hypothalamic SO & PV nuclei Hypothalamic median eminence ADENOHYPOPHYSIS Pars distalis Pars tuberalis NEUROHYPOPHYSIS Infundibular stem neural part of stalk1 3 2 1 2 3 Cysts Cysts in Pars intermedia - remnants of Rathke’s pouch lumen? Rathke’s pouch lumen
48 Pars nervosa/ Infundibular process Pars intermedia Hypothalamic SO & PV nuclei Hypothalamic median eminence ADENOHYPOPHYSIS Pars distalis Pars tuberalis NEUROHYPOPHYSIS Infundibular stem/ neural part of stalk1 3 2 1 2 3 Cysts Cysts in Pars intermedia - remnants of Rathke’s pouch lumen?
49 Posterior Pituitary Gland • Pituitary gland hangs by a stalk from the hypothalamus of the brain. – anterior pituitary - appears glandular – posterior pituitary - appears fibrous • Neurons produce antidiuretic hormone (ADH) and oxytocin. – stored in, and released from, the posterior pituitary gland in response to neural stimulation from the hypothalamus
50 Effects of ADH
51 Anterior Pituitary Gland • Develops from a pouch of epithelial tissue that pinches off the roof of the embryo’s mouth. – produces the hormones it secretes:  growth hormone (GH) stimulates muscles and bones to grow  adrenocorticotropic hormone (ACTH) regulates glucose homeostasis  thyroid-stimulating hormone (TSH) stimulates the production of thyroxin by thyroid gland  luteinizing hormone (LH) ovulation and testosterone production in testes  follicle-stimulating hormone (FSH) develops ovarian follicle and sperm in males  prolactin (PRL) stimulates mammary glands to produce milk  melanocyte-stimulating hormone (MSH) synthesis and dispersion of melanin pigment
52 Major Pituitary Gland Hormones
53 Anterior Pituitary Gland • Hypothalamic control of anterior pituitary gland secretion – Neurons in the hypothalamus secrete releasing hormones and inhibiting hormones into blood capillaries at the base of the hypothalamus.  Each hormone delivered by hypothalamohypophysial portal system regulates secretion or inhibition of a specific anterior pituitary hormone.
54 Neurons in the hypothalamus secretes hormones that are carried by short blood vessels directly to the ant. Pituitary gland, where they either stimulate or inhibit the secretions of the ant pituitary hormones Cell body Axons to primary capillaries Primary capillaries Pituitary stalk Posterior pituitary Anterior pituitary Secondary capillaries Portal venules
55 Anterior Pituitary Gland • Negative feedback inhibition acts to maintain relatively constant levels of the target cell hormone. – Positive feedback cannot maintain constancy of the internal environment.
56 Negative Feedback Inhibition Hormones secreted by some endocrine glands feed back to inhibit the secretion of hypothalamic releasing hormones and anterior pituitary hormones
57 Thyroid and Parathyroid Glands • Thyroid gland – Shaped like a shield and lies just below the Adam’s apple in the front of the neck.  Thyroxine helps set basal metabolic rate by stimulating the rate of cell respiration.  In children, thyroid hormones also promote growth and stimulate maturation of the central nervous system.  unique function in amphibians - metamorphosis from larvae into adults
58 Regulation of Thyroxine Secretion
59 Thyroid and Parathyroid Glands • Parathyroid gland and calcium homeostasis – four small glands attached to the thyroid  produces parathyroid hormone (PTH)  one of only two hormones in humans that are absolutely essential for survival  stimulates osteoclasts in bone to dissolve calcium phosphate crystals and release Ca++ into the blood
60 Regulation of Blood Calcium Levels
61 Calcium Metabolism: Figure 23-20: Calcium balance in the body
62Figure 19.20
63 THYROID GLAND Follicular cells simple cuboidal epithelium Colloid / Thyroglobulin glycoprotein = PAS+ Follicles for storage C cells/ Parafollicular cells Capillaries In the section, the follicles do not hold their spherical shape this well, and the colloid displays knife chatters and variable staining
64 THYROID GLAND: Physiological variablity Follicular cells high cuboidal when very active; squamous when inactive Colloid / Thyroglobulin less in active state, excessive in goitre Follicles - size varies inversely with activity C cells/ Parafollicular cells for calcitonin Capillaries
65 GOLGI Amino acids Sugars Iodine Thyroglobulin Endocytosis Cleavage Release of hormones T3 & T4 Synthesis & iodination of thyroglobulin THYROID FOLLICULAR CELL TSH
66 Goiter • Both hypo and hyperthyroidism can have goiter as a symptom • Goiter is a swelling of the neck due to hypertrophy of the thyroid gland • How can one explain that?
67 Goiter in hypothyroidism • Most often due to a lack of dietary iodine • The thyroid hormone is unable to synthesize a functional thyroid hormone (T3 and T4) • The person express symptoms of hypothyroidism • The nonfunctional T3/T4 cannot promote a negative feedback on TRH and TSH   the hypotalamus and pituitary gland increase their secretions  the thyroid gland is stimulated to secrete more T3 and T4 … • In children, the lack of functional T3/T4 result in cretinism, a form a mental retardation
68 Goiter in hyperthyroidism • The cells secreting TRH or TSH on the hypothalamus and pituitary gland (respectively) have become abnormal and no longer are sensitive to the negative feedback  they continue to secrete TRH or TSH  continuous stimulation of the thyroid gland with excess thyroid hormones being formed   symptoms of hyperthyroidism
69 PARATHYROID GLAND Oxyphil cells Chief cells Characteristic is the lack of obvious general structural features Small, pale, resemble lymphocytes, but have more cytoplasm Larger, eosinophilic, darker nuclei, packed with mitochondria
70 PARATHYROID GLAND OXYPHIL CELLS CHIEF CELLS have membrane calcium sensors to respond to low Ca2+ by releasing parathyroid hormone /PTH. PTH stimulates osteoclasts to release Ca2+ from bone & has conserving renal effects derivatives of Chief cells
71 Osteoclast Ruffled border agitating released enzymes & acid Eaten-out hole is a Howship’s lacuna BONE REMODELING Osteoclasts as a team eating out a resorption tunnel Sealing ring of tight attachment to bone BONE MATRIX BONE
72 ONCOCYTIC CONVERSION As cuboidal epithelia and glands age, a few of their epithelial cells lose most of their normal organelles and fill up with mitochondria. Mitochondria-rich cells are eosinophilic. This event results in two classes of cell: those that are functioning normally and need many mitochondria - gastric parietal cells, renal proximal-tubular cells, striated-duct cells, etc; & non-functional mitochondria-stuffed cells in older epithelia. These have acquired two names: the usual - oncocyte, and, as an exception, the archaic oxyphil cell in the parathyroids. & Hurthle cells in thyroid :
73 Adrenal Glands • Adrenal glands are located above each kidney. – Each gland composed of inner portion (adrenal medulla) and outer layer (adrenal cortex). • Adrenal medulla – receives neural input from axons of sympathetic division of the autonomic nervous system, and secretes epinephrine and norepinephrine in response
74 Adrenal Glands • Adrenal cortex – Hormones from adrenal cortex are collectively referred to as corticosteroids.  Cortisol maintains glucose homeostasis, and modulates some aspects of the immune response.  Aldosterone stimulates the kidneys to reabsorb Na+ and secrete K+ into the urine.
75 Adrenal Glands
76 Cortex Medulla Capsule Adrenal vein ADRENAL/SUPRARENAL GLAND The adrenal embryologically is a composite of the: medulla derived from ectoder mal neural-crest cells; & cortex formed from mesoder m next to the mesonephros
77 ADRENAL CORTEX Cortex Zona glomerulosa Zona fasciculata Zona reticularis ] ] small balls of cells straight bundles of paler cells cords of cells in a network sparse Stroma of reticular fibers & vessels Capsule
78 ADRENAL CORTICAL HORMONES Cortex Zona glomerulosa Zona fasciculata Zona reticularis ] ] makes mineralocorticoids, e.g., aldosterone makes glucocorticoids, e.g., cortisol makes sex steroids, e.g., androstenedione
79 Zona glomerulosa regulated by Renin-angiotensin system Zona fasciculata driven by ACTH Zona reticularis driven by LH & ACTH ] ] to make & release mineralocorticoids to make glucocorticoids to make sex steroids* & glucocorticoids Zona-fasciculata steroid-synthesizing cell Cholesterol droplets (often dissolved out) Smooth ER, often tubular (bag-of-worms visual effect) Mitochondria with tubular cristae dehydroepiandrosterone*
80 Zona glomerulosa regulated by Renin-angiotensin system mineralocorticoids glucocorticoids sex steroids* & glucocorticoids ] ] Zona reticularis driven by LH & ACTH Zona fasciculata driven by ACTH
81 Zona-fasciculata steroid-synthesizing cell Cholesterol droplets (often dissolved out) Smooth ER, often tubular (bag-of-worms visual effect) Mitochondria with tubular cristae Inner mitochondrial membrane has a P450 enzyme for steroid biosynthesis
82 Zona glomerulosa ] JG cells Renin Converting Enzyme DISTAL TUBULE Angiotensinogen Angiotensin I Angiotensin II Aldosterone Vasoconstriction Sodium + water reabsorption (so blood pressure up) JUXTAGLOMERULAR APPARATUS 6 Outside kidney Renin is a protease
83 Aldosterone Zona glomerulosa JG cells Renin Converting Enzyme/ ACE Angiotensinogen Angiotensin I Angiotensin II Vasoconstriction RENIN-ANGIOTENSIN SYSTEM DISTAL TUBULE Outside kidney ACE is in many tissues, and the angiotensin II receptor is widespread, so that the RA system is very endocrine in affecting most of the body, not just vessels, adrenal & kidney
84 ADRENAL MEDULLA Chromaffin cells Sympathetic axons Central vein Occasional neuron terminating mainly on chromaffin cells Chromaffin cells so named, because of chromaffin reaction - a brown darkening of medulla seen when catecholamines react with dichromate & other oxidising agents
85 ADRENAL MEDULLA Chromaffin cells make epinephrine & norepinephrine Sympathetic axons Central vein Occasional neuron terminating mainly on chromaffin cells Epinephrine & norepinephrine are catecholamines stored, in association with the protein chromogranin, in dense- cored granules/ vesicles. E & NE augment sympathetic autonomic nervous-system actions
86 CATECHOLAMINE SYNTHESIS Chromaffin cells make epinephrine & norepinephrine TYROSINE tyrosine hydroxylase DOPA/Dihydroxyphenylalanine DOPAMINE aromatic L-amino acid decarboxylase/AADC dopamine β-hydroxylase/DBH NOREPINEPHRINE EPINEPHRINE/Adrenalin phenylethanolamine-N-methyltransferase [rate-limiting?]
87Figure 6.12b
88Figure 21.15
89 Adrenal gland hormones Regulation Glands Hormones Target organs Action Pathology Reflex Adrenal medulla Epinephrine ANS target organs Fight/flight Stress Blood Pressure Adrenal cortex - Mineralocorticoid = aldosterone DCT from renal tubule - promote sodium reabsorption Not enough" Addison disease CRH  ACTH Glucocorticoid = cortisone Many cells Mobilize fuels – stress adaptation Excess hormone: Cushing syndrome GnRH  GN Estrogen Testosterone Sexual organs - Sex organ maintenance - Gamete development Infertility
90
91 Pancreas • Located adjacent to the stomach and is connected to the duodenum by the pancreatic duct. – Secretes bicarbonate ions and a variety of digestive enzymes into small intestine.  β cells of islets of Langerhans secrete insulin, and α cells secrete glucagon.  antagonistic  Insulin lowers while glucogen raises blood glucose.
92 PANCREAS Duodenum Exocrine acini digestive enzymes Lobule } Endocrine islet metabolic hormones Ducts alkaline ions Enteroendocrine cells hormones
93 Islet of Langerhans ISLET: Cell types & products Beta cell - insulin (majority) Alpha cell - Glucagon Delta cell - Somatostatin PP cell - Pancreatic polypeptide Beta & Alpha cells are directly sensitive to glucose level
94 Antagonistic Actions of Insulin and Glucagon
95 Glucose regulation • Glucose level controlled by insulin and glucagon • Insulin promotes a decrease in blood glucose • Glucagon promotes an increase in blood glucose
96 Glucose regulation
97Figure 3.21 Fate of glucose
98 Diabetes mellitus • Type I: autoimmune disease  beta cells of the islets of Langerhans are destroyed by antibodies • Type II: The cells become insulin-resistant  glucose does not enter the cells as readily
99 Diabetic foot
100 Other Endocrine Glands • Ovaries and testes – produce androgen  secondary sexual characteristics • Pineal gland – secretes melatonin  regulates biological clocks
101 Other Endocrine Glands • Molting and metamorphosis in insects – Hormone secretions influence both molting and metamorphosis in insects.  Brain hormone stimulates production of ecdysone (molting hormone).  high levels cause molting to occur  juvenile hormone  high levels prevent transformation to an adult
102 Other Endocrine Glands • Endocrine disrupting chemicals – chemicals that interfere with hormone function  Any chemical that can bind to receptor proteins and mimic the effects of the hormone is called a hormone agonist.  Any chemical that binds to receptor proteins and has no effect, but blocks the hormone from binding is a hormone antagonist.
103 Cerebral Cortex Cerebellum Pineal gland Brain Stem Eye & optic nerve Central sympathetic pathways Suprachiasmatic nucleus Thoracic cord Sympathetic preganglionic S Cervical ganglion Sympathetic postganglionics PINEAL ACTIVATION PATHWAY 1 3 4 2 5 7 Darkness increases HIOMT enzyme to make melatonin HydroxyIndole-O-MethylTransferase 1 7 6
104 Cerebral Cortex Cerebellum Pineal gland Brain Stem Eye & optic nerve Central sympathetic pathways Suprachiasmatic nucleus Thoracic cord Sympathetic preganglionic S Cervical ganglion Sympathetic postganglionics PINEAL ACTIVATION PATHWAY 1 3 4 2 5 6 1 7 7 melatonin light off Melanopsin in retinal ganglion cells is the photosensitive mediator
105 Cerebral Cortex Cerebellum PINEAL GLAND Brain Stem Eye & optic nerve Central sympathetic pathways Suprachiasmatic nucleus Thoracic cord Sympathetic preganglionic S Cervical ganglion Sympathetic postganglionics PINEAL ACTIVATION PATHWAY 1 3 4 2 5 7 Darkness increases HIOMT enzyme to make melatonin HydroxyIndole-O-MethylTransferase 6 melatonin light off
106 cvlAl re uo - - - - - - - ENDOCRINE ORGANS II Plus neuroendocrine cells developed within mature gut, airway, etc epithelia [Kidney] [Heart] ANF EPO Renin VIP Gastrin Secretin, etc Gonads [Placenta] hCG Estrogen Progesterone Sex steroids [Adipose tissue] Leptin
107 ATRIAL HEART & ANF Atrial myocytes have a well developed Golgi complex and secretory granules Reticular fiber Atrial Natriuretic Factor (ANF) in the granules STIMULATES: diuresis; sodium excretion (natriuresis); vasorelaxation; & INHIBITS the Renin-Angiotensin system & aldosterone secretion
108 Enteroendocrine cell types I Enteroendocrine cell small, pale, few; granules are located basally for release into the lamina propria Entero is misleading because: some cell types are confined to the stomach; and peptides & amines are signaling agents in other epithelia and other systems e.g. brain G cell - gastrin S cell - secretin I cell - cholecystokinin ECL cell - histamine D cell (antral) - somatostatin EC cell - serotonin A cell - ghrelin
109 Enteroendocrine cell types II Motilin cell: why not ‘M’ cell? There already is one, involved in immunity G cell - gastrin S cell - secretin I cell - cholecystokinin ECL cell - histamine L cell - glucagon-like peptide (GLP-1 & 2) peptide Y (PYY) oxyntomodulin K cell - gastric inhibitory polypeptide/GIP N cell - neurotensin M? cell - motilin D cell (antral) - somatostatin Coordinated with extrinsic & intrinsic neural controls and interacting amongst themselves EC cell - serotonin A cell - ghrelin
110 EXOCRINE PANCREAS Controls Duodenum Exocrine aciniEnteroendocrine cells Secretin & CCK digestive enzymes HCO3 - ions RESPONSE Acid Fats Peptides STIMULI CONTROLLER + Vagal cholinergic control
111 SOURCES OF ‘GUT’ HORMONES RECTUM LIVER PANCREAS GALL BLADDER STOMACH SMALL GUT LARGE GUT Bile gastrin ghrelin Duodenum cholecystokinin motilin somatostatin neurotensin GIP-1 GLP-1&2 Peptide Y insulin glucagon PPY somatostatin secretin Oxyntomodulin
112 SOURCES OF ‘GUT’ HORMONES PANCREAS STOMACH SMALL GUT LARGE GUT gastrin ghrelin Duodenum cholecystokinin motilin somatostatin neurotensin GIP-1 GLP-1&2 Peptide Y insulin glucagon PPY somatostatin secretin Oxyntomodulin
113 Enteroendocrine cell types III Immunostaining for the peptide or chromogranin and fluorescence methods for the amine derivatives now provide clear identification of the cells, but against a background of the old silver-based cell nomenclature A messy story*, because of the various staining reactions of enteroendocrine cells (particularly with silver methods) based on the peptide hormones, the associated chromogranin storage protein in the granules, and any catecholamine, serotonin or histamine content. ECL cell - EnteroChromaffin-Like cell
114 Adipocyte hormones & other metabolic players RECTUM LARGE GUT LIVER SMALL GUT STOMACH PANCREAS GALL BLADDER E S O P H A G U S MOUTH APPENDI X SALIVARY GLAND AIRWAY HYPOTHALAMUS Appetites Homeostasis Emotion CEREBRAL CORTEX Cerebellum Pons Mid- brain Medulla PITUITARY TALUS CALCANEUS Metatarsa l FEMUR Fat cell Adipocytes MUSCLE
115 Adipocyte hormones - LIVER HYPOTHALAMUS TALUS CALCANEUS Metatarsa l FEMUR Fat cell Adipocytes MUSCLE LEPTIN ADIPONECTIN for energy balance and glucose homeostasis
116 Visceral/abdominal fat & type II diabetes, etc LIVER HYPOTHALAMUS TALUS CALCANEUS Metatarsa l FEMUR Fat cell Adipocytes MUSCLE LEPTIN ADIPONECTIN MACROPHAGES(MΦs) Macrophages accumulate in the stroma of the fatty tissue, become activated to release abnormal cytokines , e.g., TNF- α ,that disrupt many metabolic pathways so that the visceral adipose tissue is permanently inflamed and dangerous, e.g. Adipocyte production of adiponectin falls Insulin signalling goes bad, etc.
117 TESTIS & LEYDIG CELLS Peritubular myoid cells LEYDIG INTERSTITIAL CELLS Acidophil Much smooth ER Lipid droplets Crystals of Reinke SERTOLI CELLS Sperm layered SPERMATOGENIC CELLS {stratified germinal epithelium BASAL LAMINA SEMINIFEROUS TUBULE SEMINIFEROUS TUBULE
118 HORMONES PITUITARY GONADOTROPHS HYPOTHALAMIC NEURONS INTERSTITIAL CELLS SEMINIFEROUS TUBULE PENIS SEMINAL VESICLE PROSTATE RETE TESTIS TUBULUS RECTUS EFFERENT DUCT EPIDIDYMIS DUCTUS DEFERNS BULBOURETHRAL GLAND urethra Androgens Courtship & Coital behaviors GnRHFSH LH 1 2 3 4 5 Secondary sexual characters 6 7 Somatic growth & metabolism

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Endocrine system

  • 1.
  • 2.
    2 Outline • Types ofRegulatory Molecules • Endocrine Glands and Hormones • Paracrine Regulation • Hormones That Enter Cells • Hormones That Do Not Enter Cells • Posterior and Anterior Pituitary Gland • Thyroid and Parathyroid Glands • Adrenal Glands • Other Endocrine Glands
  • 3.
    3 SIGNALING AGENTS &FACTORS Neurotransmitters Peptides Oxygen-based molecules, e.g., NO Prostanoids Hormones Cytokines ( some are Chemokines) Extracellular-matrix molecules Nutrients & metabolites Mechanical stimuli, e.g., fluid shear Cell-surface glycoproteins Hormones from endocrine cells & organs are part of a much larger picture of the outside controls on cells Heat, osmolarity, exogenous chemicals, etc ENDOCRINE
  • 4.
    4 Types of RegulatoryMolecules • Hormone – A regulatory chemical secreted into the blood by an endocrine gland, or an organ exhibiting endocrine function. • Target Cells respond to hormone – Neurohormone – A chemical messenger secreted by neuron into the blood rather than the synaptic cleft. • Paracrine - regulatory molecules work without being transmitted by the blood – not endocrine • Pheromone - communication messengers
  • 5.
    5 Copyright © TheMcGraw-Hill Companies, Inc. Permission required for reproduction or display. Axon Neurotransmitter Endocrine gland Paracrine regulator Receptor proteins Hormone carried by blood Target cell
  • 6.
    6 Endocrine Glands andHormones • Hormones secreted by the endocrine glands belong to four chemical categories: – Polypeptides - short chains of amino acids less than 100 amino acids (insulin & ADH) – Glycoproteins- longer than100 A.A. with carbs (FSH and LH) – Amines - Amines – A.A. derived from tyrosine and tryptophan – epinephrine and norepinephrine and melatonin – Steroids - lipids derived from cholesterol  sex steroids - testosterone, estadiol, progesterone, and cortisol – secreted by testes, ovaries, placenta and adrenal cortex  Corticosteroids - adrenal cortex cortisol and aldosterone (regulates glucose and salt balance) – All hormones can be categorized as lipophilic (fat soluble) or hydrophilic (water soluble).
  • 7.
    7 Endocrine Glands andHormones • Neural and endocrine interactions – Endocrine system also interacts and cooperates with the nervous system to regulate the activities of the other organ systems of the body. – Secretory activity of many endocrine glands controlled by nervous system like  Adrenal medulla, posterior pituitary, and pineal gland  major site for neural regulation is the brain’s regulation of the anterior pituitary by the hypothalmus However many are not under neural control
  • 8.
  • 9.
    9 cvlAl re u o - - -- - - - diaphragm Parathyroids Adrenal cortex Thyroid Pituitary anterior Pancreas Gonads ENDOCRINE ORGANS I
  • 10.
    10 [ non-epithelial origin] cvlAl re uo - - - - - - - diaphragm Parathyroids Adrenal cortex Thyroid Pituitary anterior Pancreas Gonads ENDOCRINE ORGANS II [Pineal] [Heart] [Adrenal medulla] [Kidney] [Placenta] Plus neuroendocrine cells developed within mature gut, airway, etc epithelia [Pituitary, posterior & Brain] [Adipose tissue]
  • 11.
    11 TYPICAL ENDOCRINE GLAND- Context hormone release vessels Clumps of endocrine cells blood control Capillary diffusion TARGET ORGAN Target cells, with receptors for binding 12 transport3 4 5 Target cells’ response 6 Feedback
  • 12.
    12 GLAND(S) WHERE CELLTYPES HORMONES SPECIAL Thyroid Neck Follicular cells C cells Thyronine Calcitonin Follicles for storage Parathyroid Neck Chief cells Parathormone /PTH Small Adrenal medulla Over kidney Chromaffin cells Epinephrine Norepinephrine Nerve fibers Adrenal cortex Over kidney Zona glomerulosa Zona fasciculata Zona reticularis Mineralocorticoids Glucocorticoids Sex steroids Pineal Brain’s center Pinealocytes Melatonin Connected for light drive Zones ENDOCRINE ORGANS I
  • 13.
    13 GLAND(S) WHERE CELLTYPES HORMONES SPECIAL Pituitary posterior Axons of PV & SO hypothal. neurons Oxytocin Vasopressin /ADH Extension of brain Pancreas Left upper quad Beta, Alpha, Delta, PP cells Insulin Glucagon Somatostatin Pancr Peptide Gonads Pelvic/ Scrotal Granulosa, Theca Lutein, & Leydig Sex steroids Inhibin Placenta Uterus Syncytiotrophoblast Female: for amplified hormonal responses Female: cyclic Pituitary anterior Below brain MTs STs GTs THs CTs Blood drains hypothal.- pituitary for control Prolactin GH LH FSH TSH ACTH Below brain Islets +Pituicytes s ENDOCRINE ORGANS II
  • 14.
    14 Paracrine Regulation • Signalingbetween cells - Local effect and short-lived occurs in many organs • Regulatory molecules – cytokines - regulate different cells of the immune system – growth factors - promote growth and cell division in specific organs – stimulate cell division at target cells
  • 15.
    15 Paracrine Regulation • Prostaglandins– most diverse group of paracrine regulators • participate in regulation of: – immune system – inflammation, pain and fever – reproductive system – reproductive function ovulation, labor, – digestive system – inhibit gastric secretions, incrfease motility and fluid absorption – respiratory system - blood vessels constriction and dilation in lungs – circulatory system - blood platelets in blood clotting – urinary system - renal blood flow vasodilation increasing urine excretion • Prostaglandin synthesis inhibited by aspirin. – nonsteroidal anti-inflammatory drug  Ibuprofen  Work to inhibit inflammation and pain by inhibiting enzyme necessary to produce prostaglandins – (cyclooxygenase -2)
  • 16.
    16 Hormones That EnterCells • Lipophilic hormones pass through the target cell’s plasma membrane and bind to intracellular receptor proteins. – hormone receptor complex then binds to specific regions of DNA  activate genes and regulate target cells
  • 17.
  • 18.
    18 Hormones That DoNot Enter Cells • Hormones that are too large or too polar to cross plasma membranes include all of the peptide and glycoprotein hormones, as well as catecholamine hormones epinephrine and norepinephrine. – bind to receptor proteins located on the outer surface of the plasma membrane  cyclic AMP second-messenger system  IP3/CA++ second-messenger system
  • 19.
    19 Action of Epinephrineon a Liver Cell 1. Epinephrine is lipophobic and needs to bind to specific receptor proteins on cell surface. 2. Acting through intermediary G proteins the hormone bound receptor activates the enzyme adenenylyl cyclase which converts ATP to cAMP 3. Cyclic AMP performs as a 2ndary messenger and activates protein kinase-A an enzyme that was previously inactive 4. Protein kinase–A phosphorylates and activates the enzyme phosphorylase which catalyses the hydrolysis of glycogen into glucose.
  • 20.
    20 IP3/CA++ Second-Messenger System 1. Thehormone epinephrine binds to specific receptor proteins on the cell surface. 2. Acting through G- proteins, the hormone-bound receptor activates the enzyme phospholipase C, which converts membrane phospholipids into inositol triphosphate (IP3) 3. IP3 diffuses thru the cytoplasm and binds to receptors on the endoplasmic reticulum 4. The binding of IP3 to the receptor stimulates the endoplasmic reticulum to release Ca++ into the cytoplasm 5. Some of the released Ca++ binds to the receptor protein called calmodulin 6. The Ca++/Calmodulin complex activates other intracellular proteins – producing the horomone effects
  • 21.
    21 Primary endocrine organs •Hypothalamus and pituitary gland secrete hormones and regulate other endocrine organs. They are the main regulatory organs of the endocrine system.
  • 22.
    22 Hypothalamus • Located belowthe thalamus and above the pituitary gland (=epiphysis) • Regulates the pituitary gland secretions through two different mechanisms
  • 23.
    23 Hypothalamus - neurohypophysis •1- Neurons, receiving information from receptors, fire APs which travel down to the post pituitary gland and stimulate the release of stored neurohormones – Oxytocin (OT) and anti- diuretic hormone (ADH)
  • 24.
    24 Hormones of theposterior pituitary Regulation Hormone Target organ Action Pathology Reflex Oxytocin - Uterus (smooth muscle) - breast tubules (smooth muscles) -labor and delivery - milk-let down -- -- Reflex (osmoreceptor) ADH (vasopressin) - DCT in kidney tubules - promote H2O reabsorption - not enough: diabetes insipidus - too much: ↑ BP?
  • 25.
    25 Hypothalamus – adenohypophysis •2- Upon stimulation, secretory cells located in the hypothalamus secrete “releasing” hormones which travel down a capillary bed toward the anterior pituitary gland (adenopituitary). Each type of releasing hormones will stimulate the secretion and release of a pituitary hormone. • Hormones which control the secretion of other hormones are tropic hormones (found in hypothalamus and pituitary gland
  • 26.
    26Figure 6.5 Hormones ofthe hypothalamus and anterior pituitary gland
  • 27.
    27Figure 6.8 Anterior pituitary RegulationHormone Target organ Action Pathology GHRH and GHIH Growth hormone (GH) Many cells (bones..) Stimulate cell growth and cell division - not enough: children  pituitary dwarfism too much: gigantism (children) – acromegaly (adult) PRH - PIH Prolactin (PL) Breast secretory cells - milk secretion -- TRH Thyroid stimulating hormone (TSH) Thyroid gland - promote thyroid gland secretion (T3 and T4) - not enough: hypothyroidism (cretinism in children) - too much: hyperthyroidism CRH Adrenocorticotropic hormone (ACTH) Adrenal cortex (3 layers) - stimulates secretion of adrenal cortex - not enough: Addison's disease - too much: Cushing syndrome GnRH Gonadotropin - Follicle stimulating hormone (FSH) - Luteinizing hormone (LH) Stimulate gamete maturation Stimulate gonadal gland secretion and gamete formation - infertility
  • 28.
    28 Figure 23-17 Same Individualwith Acromegaly (evolution over 20 years)
  • 29.
  • 30.
    30 HYPOPHYSIS/ Pituitary gland Pituitarystalk Posterior lobe Hypoth alamus Anterior lobe Dura IIIrd Ve Intermediatelobe
  • 31.
    31 Pars nervosa Infundibular process Pars intermedia PITUITARYSUB-DIVISIONS Hypothalamic SO & PV nuclei Hypothalamic median eminence ADENOHYPOPHYSIS Pars distalis Pars tuberalis NEUROHYPOPHYSIS Infundibular stem neural part of stalk 1 3 2 1 2 3
  • 32.
    32 Unlike some otherendocrine cells, those of the anterior pituitary separate their supplying a hormone from the detection of the need for the hormone. The sensitivity to need is performed by hypothalamic neurons, which can coordinate requirements for several hormones with drives, and events outside the person. Anterior-pituitary cells & hormones The system also allows for control by inhibitory factors, as well as + driving hormone-releasing factors
  • 33.
    33 HYPOTHALAMO-HYPOPHYSEAL Portal flow Superiorarteries Portal drainage Hypothalamus Anterior lobe capillaries Dura Hypothalamic capillary bed Neurosecretory neurons Veins 1 2 3 4 5 A portal flow takes venous blood drained from one organ and uses it as a supply to another organ, e.g., gut to liver
  • 34.
    34 HYPOTHALAMO-HYPOPHYSEAL Portal flow Superiorarteries Portal drainage Hypothalamus Anterior lobe capillaries Hypothalamic capillary bed Neurosecretory neurons Veins 1 2 3 4 5 Portal flow carries factors from hypothalamic neurons to pituitary anterior-lobe cells E.g.,TH-RF from neuron causes Thyrotroph to release TSH
  • 35.
    35 Superior arteries Portal drainage Hypothalamus Anteriorlobe capillaries Hypothalamic capillary bed Neurosecretory neurons Veins 1 2 3 4 5 Mammotrophs MTs Somatotrophs STs Gonadotrophs GTs Thyrotrophs THs Corticotrophs CTs Blood drains hypothalamus-pituitary for control by RFs, etc Prolactin PRL Growth hormone GH Luteinizing hormone LH Follicle-stimulating hormone FSH Thyroid-stimulating hormone TSH Adrenocorticotrophic hormone ACTH Anterior-pituitary cells & hormones
  • 36.
    36 Mammotrophs MTs Somatotrophs STs GonadotrophsGTs Thyrotrophs THs Corticotrophs CTs Blood drains hypothalamus- pituitary for control by RFs, etc Prolactin PRL Growth hormone GH Luteinizing hormone LH/ICSH Follicle-stimulating hormone FSH Thyroid-stimulating hormone TSH Adrenocorticotrophic hormone ACTH cleaved from pro-opio-melanonocortin/ POMC Anterior-pituitary cells & hormones Acidophil Basophil
  • 37.
    37 Anterior-pituitary cells 2 MammotrophsMTs Somatotrophs STs Gonadotrophs GTs Thyrotrophs THs Corticotrophs CTs Prolactin PRL Growth hormone GH Luteinizing hormone LH FSH TSH ACTH Acidophil Basophil Chromophobe Chromophobes stain weakly, in comparison to CHROMOPHILS - Acidophils & Basophils Folliculo-Stellate cells lie amongst the glandular cells; doing what?
  • 38.
    38 Anterior-pituitary cells 3 CorticotrophsCTs ACTH but by selective enzymatic cleavage of a larger 32kDa precursor - pro-opiomelanocortin, also made in the hypothalamus and elsewhere, and there serving to provide other hormones & neurotransmitters Pro-opiomelanocortin ACTH Pro-ACTH β-LPH β-Endorphin β- MSH SP simplified POMC ~ Pro-opiomelanocortin
  • 39.
    39 Anterior-pituitary cells 4 Selectiveenzymatic cleavage of the precursor - pro- opiomelanocortin, provides other hormones & transmitters ACT H β-Endorphin Pro-opiomelanocortinSP NT 1-76 β-LPHACTH β-LPHACTH γ-LPH NT 1-49 JP γ -MSH α-MSH β-MSH elaborate MSH ~ Melanocyte-stimulating hormone NT ~ amino-terminal peptides LPH ~ Lipotropic hormone Pro-hormone convertase 1 Pro-hormone convertase 1 Pro−γ -MSH Pro−γ -MSH After Reudelhuber TL. J Clin Invest 2003;111:1115-1116
  • 40.
    40 NEUROHYPOPHYSIS Pars nervosa Hypothalamic SO& PV nuclei Supraoptic & Paraventricular nuclei Hypothalamus 1 2 3 Inferior arteries Veins Release of hormone is separated from production * * * * Neural stalk Optic chiasm
  • 41.
    41 NEUROHYPOPHYSIS Pars nervosa Hypothalamic SO& PV nuclei Supraoptic & Paraventricular nuclei Hypothalamus 1 2 3 Inferior arteries Veins * * Neural stalk Optic chiasm Note - the supraoptic nucleus is above the optic nerve & chiasm, but closer to the chiasm is the small suprachiasmatic nucleus (relaying the darkness stimulus indirectly to the pineal gland).
  • 42.
    42 NEUROHYPOPHYSIS Pars nervosa axons,terminals, pituicytes & capillaries Hypothalamic SO & PV nucleiHypothalamus Infundibular stem neural part of stalk - axons & glia 1 2 3 Neurosecretory neurons producing oxytocin & vasopressin/ADH Inferior arteries Veins Release of hormone is separated from production * * * *
  • 43.
    43 NEUROHYPOPHYSIS Hypothalamic SO &PV nucleiHypothalamus Neurosecretory neurons producing oxytocin & vasopressin/ADH Inferior arteries Veins Hormone travels down the axon bound to the carrier protein - neurophysin, from which it is cleaved for release * *
  • 44.
    44 SUCKLING REFLEX Hypothalamic SO& PV neuron activation Hypothalamus * BREAST Myoepithelial-cell contraction Sensory response Oxytocin release Stimulus1 2 3 4 56 7 Milk ejectionVascular transfer
  • 45.
    45 PITUITARY Mid-sagittal sectionof 1-m embryo STOMODEUM PHARYNGEAL ARCHES PITUITARY RATHKE’S POUCH starting in oral ectoderm BRAIN I II
  • 46.
    46 PITUITARY DEVELOPMENT II Neural-tubediencephalic ectoderm Oral-pharyngeal lining ectoderm IIIrd Ve Rathke’s pouch Pars tuberalis Pars distalis Pars intermedia Pars nervosa Infundibular stem Hypothalamus ADENOHYPOPHYSIS NEUROHYPOPHYSIS
  • 47.
    47 PITUITARY DEVELOPMENT II Parstuberalis Pars distalis Pars intermedia Pars nervosa Infundibular stem Hypothalamus Pars nervosa Infundibular process Pars intermedia Hypothalamic SO & PV nuclei Hypothalamic median eminence ADENOHYPOPHYSIS Pars distalis Pars tuberalis NEUROHYPOPHYSIS Infundibular stem neural part of stalk1 3 2 1 2 3 Cysts Cysts in Pars intermedia - remnants of Rathke’s pouch lumen? Rathke’s pouch lumen
  • 48.
    48 Pars nervosa/ Infundibular process Parsintermedia Hypothalamic SO & PV nuclei Hypothalamic median eminence ADENOHYPOPHYSIS Pars distalis Pars tuberalis NEUROHYPOPHYSIS Infundibular stem/ neural part of stalk1 3 2 1 2 3 Cysts Cysts in Pars intermedia - remnants of Rathke’s pouch lumen?
  • 49.
    49 Posterior Pituitary Gland •Pituitary gland hangs by a stalk from the hypothalamus of the brain. – anterior pituitary - appears glandular – posterior pituitary - appears fibrous • Neurons produce antidiuretic hormone (ADH) and oxytocin. – stored in, and released from, the posterior pituitary gland in response to neural stimulation from the hypothalamus
  • 50.
  • 51.
    51 Anterior Pituitary Gland •Develops from a pouch of epithelial tissue that pinches off the roof of the embryo’s mouth. – produces the hormones it secretes:  growth hormone (GH) stimulates muscles and bones to grow  adrenocorticotropic hormone (ACTH) regulates glucose homeostasis  thyroid-stimulating hormone (TSH) stimulates the production of thyroxin by thyroid gland  luteinizing hormone (LH) ovulation and testosterone production in testes  follicle-stimulating hormone (FSH) develops ovarian follicle and sperm in males  prolactin (PRL) stimulates mammary glands to produce milk  melanocyte-stimulating hormone (MSH) synthesis and dispersion of melanin pigment
  • 52.
  • 53.
    53 Anterior Pituitary Gland •Hypothalamic control of anterior pituitary gland secretion – Neurons in the hypothalamus secrete releasing hormones and inhibiting hormones into blood capillaries at the base of the hypothalamus.  Each hormone delivered by hypothalamohypophysial portal system regulates secretion or inhibition of a specific anterior pituitary hormone.
  • 54.
    54 Neurons in thehypothalamus secretes hormones that are carried by short blood vessels directly to the ant. Pituitary gland, where they either stimulate or inhibit the secretions of the ant pituitary hormones Cell body Axons to primary capillaries Primary capillaries Pituitary stalk Posterior pituitary Anterior pituitary Secondary capillaries Portal venules
  • 55.
    55 Anterior Pituitary Gland •Negative feedback inhibition acts to maintain relatively constant levels of the target cell hormone. – Positive feedback cannot maintain constancy of the internal environment.
  • 56.
    56 Negative Feedback Inhibition Hormonessecreted by some endocrine glands feed back to inhibit the secretion of hypothalamic releasing hormones and anterior pituitary hormones
  • 57.
    57 Thyroid and ParathyroidGlands • Thyroid gland – Shaped like a shield and lies just below the Adam’s apple in the front of the neck.  Thyroxine helps set basal metabolic rate by stimulating the rate of cell respiration.  In children, thyroid hormones also promote growth and stimulate maturation of the central nervous system.  unique function in amphibians - metamorphosis from larvae into adults
  • 58.
  • 59.
    59 Thyroid and ParathyroidGlands • Parathyroid gland and calcium homeostasis – four small glands attached to the thyroid  produces parathyroid hormone (PTH)  one of only two hormones in humans that are absolutely essential for survival  stimulates osteoclasts in bone to dissolve calcium phosphate crystals and release Ca++ into the blood
  • 60.
    60 Regulation of BloodCalcium Levels
  • 61.
    61 Calcium Metabolism: Figure 23-20:Calcium balance in the body
  • 62.
  • 63.
    63 THYROID GLAND Follicular cells simplecuboidal epithelium Colloid / Thyroglobulin glycoprotein = PAS+ Follicles for storage C cells/ Parafollicular cells Capillaries In the section, the follicles do not hold their spherical shape this well, and the colloid displays knife chatters and variable staining
  • 64.
    64 THYROID GLAND: Physiologicalvariablity Follicular cells high cuboidal when very active; squamous when inactive Colloid / Thyroglobulin less in active state, excessive in goitre Follicles - size varies inversely with activity C cells/ Parafollicular cells for calcitonin Capillaries
  • 65.
    65 GOLGI Amino acids Sugars Iodine Thyroglobulin Endocytosis Cleavage Release ofhormones T3 & T4 Synthesis & iodination of thyroglobulin THYROID FOLLICULAR CELL TSH
  • 66.
    66 Goiter • Both hypoand hyperthyroidism can have goiter as a symptom • Goiter is a swelling of the neck due to hypertrophy of the thyroid gland • How can one explain that?
  • 67.
    67 Goiter in hypothyroidism •Most often due to a lack of dietary iodine • The thyroid hormone is unable to synthesize a functional thyroid hormone (T3 and T4) • The person express symptoms of hypothyroidism • The nonfunctional T3/T4 cannot promote a negative feedback on TRH and TSH   the hypotalamus and pituitary gland increase their secretions  the thyroid gland is stimulated to secrete more T3 and T4 … • In children, the lack of functional T3/T4 result in cretinism, a form a mental retardation
  • 68.
    68 Goiter in hyperthyroidism •The cells secreting TRH or TSH on the hypothalamus and pituitary gland (respectively) have become abnormal and no longer are sensitive to the negative feedback  they continue to secrete TRH or TSH  continuous stimulation of the thyroid gland with excess thyroid hormones being formed   symptoms of hyperthyroidism
  • 69.
    69 PARATHYROID GLAND Oxyphil cells Chiefcells Characteristic is the lack of obvious general structural features Small, pale, resemble lymphocytes, but have more cytoplasm Larger, eosinophilic, darker nuclei, packed with mitochondria
  • 70.
    70 PARATHYROID GLAND OXYPHIL CELLS CHIEFCELLS have membrane calcium sensors to respond to low Ca2+ by releasing parathyroid hormone /PTH. PTH stimulates osteoclasts to release Ca2+ from bone & has conserving renal effects derivatives of Chief cells
  • 71.
    71 Osteoclast Ruffled border agitating releasedenzymes & acid Eaten-out hole is a Howship’s lacuna BONE REMODELING Osteoclasts as a team eating out a resorption tunnel Sealing ring of tight attachment to bone BONE MATRIX BONE
  • 72.
    72 ONCOCYTIC CONVERSION As cuboidalepithelia and glands age, a few of their epithelial cells lose most of their normal organelles and fill up with mitochondria. Mitochondria-rich cells are eosinophilic. This event results in two classes of cell: those that are functioning normally and need many mitochondria - gastric parietal cells, renal proximal-tubular cells, striated-duct cells, etc; & non-functional mitochondria-stuffed cells in older epithelia. These have acquired two names: the usual - oncocyte, and, as an exception, the archaic oxyphil cell in the parathyroids. & Hurthle cells in thyroid :
  • 73.
    73 Adrenal Glands • Adrenalglands are located above each kidney. – Each gland composed of inner portion (adrenal medulla) and outer layer (adrenal cortex). • Adrenal medulla – receives neural input from axons of sympathetic division of the autonomic nervous system, and secretes epinephrine and norepinephrine in response
  • 74.
    74 Adrenal Glands • Adrenalcortex – Hormones from adrenal cortex are collectively referred to as corticosteroids.  Cortisol maintains glucose homeostasis, and modulates some aspects of the immune response.  Aldosterone stimulates the kidneys to reabsorb Na+ and secrete K+ into the urine.
  • 75.
  • 76.
    76 Cortex Medulla Capsule Adrenal vein ADRENAL/SUPRARENAL GLAND Theadrenal embryologically is a composite of the: medulla derived from ectoder mal neural-crest cells; & cortex formed from mesoder m next to the mesonephros
  • 77.
    77 ADRENAL CORTEX Cortex Zona glomerulosa Zonafasciculata Zona reticularis ] ] small balls of cells straight bundles of paler cells cords of cells in a network sparse Stroma of reticular fibers & vessels Capsule
  • 78.
    78 ADRENAL CORTICAL HORMONES Cortex Zonaglomerulosa Zona fasciculata Zona reticularis ] ] makes mineralocorticoids, e.g., aldosterone makes glucocorticoids, e.g., cortisol makes sex steroids, e.g., androstenedione
  • 79.
    79 Zona glomerulosa regulatedby Renin-angiotensin system Zona fasciculata driven by ACTH Zona reticularis driven by LH & ACTH ] ] to make & release mineralocorticoids to make glucocorticoids to make sex steroids* & glucocorticoids Zona-fasciculata steroid-synthesizing cell Cholesterol droplets (often dissolved out) Smooth ER, often tubular (bag-of-worms visual effect) Mitochondria with tubular cristae dehydroepiandrosterone*
  • 80.
    80 Zona glomerulosa regulated by Renin-angiotensin system mineralocorticoids glucocorticoids sexsteroids* & glucocorticoids ] ] Zona reticularis driven by LH & ACTH Zona fasciculata driven by ACTH
  • 81.
    81 Zona-fasciculata steroid-synthesizing cell Cholesteroldroplets (often dissolved out) Smooth ER, often tubular (bag-of-worms visual effect) Mitochondria with tubular cristae Inner mitochondrial membrane has a P450 enzyme for steroid biosynthesis
  • 82.
    82 Zona glomerulosa ] JGcells Renin Converting Enzyme DISTAL TUBULE Angiotensinogen Angiotensin I Angiotensin II Aldosterone Vasoconstriction Sodium + water reabsorption (so blood pressure up) JUXTAGLOMERULAR APPARATUS 6 Outside kidney Renin is a protease
  • 83.
    83 Aldosterone Zona glomerulosa JG cells Renin Converting Enzyme/ACE Angiotensinogen Angiotensin I Angiotensin II Vasoconstriction RENIN-ANGIOTENSIN SYSTEM DISTAL TUBULE Outside kidney ACE is in many tissues, and the angiotensin II receptor is widespread, so that the RA system is very endocrine in affecting most of the body, not just vessels, adrenal & kidney
  • 84.
    84 ADRENAL MEDULLA Chromaffin cells Sympatheticaxons Central vein Occasional neuron terminating mainly on chromaffin cells Chromaffin cells so named, because of chromaffin reaction - a brown darkening of medulla seen when catecholamines react with dichromate & other oxidising agents
  • 85.
    85 ADRENAL MEDULLA Chromaffin cells makeepinephrine & norepinephrine Sympathetic axons Central vein Occasional neuron terminating mainly on chromaffin cells Epinephrine & norepinephrine are catecholamines stored, in association with the protein chromogranin, in dense- cored granules/ vesicles. E & NE augment sympathetic autonomic nervous-system actions
  • 86.
    86 CATECHOLAMINE SYNTHESIS Chromaffin cellsmake epinephrine & norepinephrine TYROSINE tyrosine hydroxylase DOPA/Dihydroxyphenylalanine DOPAMINE aromatic L-amino acid decarboxylase/AADC dopamine β-hydroxylase/DBH NOREPINEPHRINE EPINEPHRINE/Adrenalin phenylethanolamine-N-methyltransferase [rate-limiting?]
  • 87.
  • 88.
  • 89.
    89 Adrenal gland hormones RegulationGlands Hormones Target organs Action Pathology Reflex Adrenal medulla Epinephrine ANS target organs Fight/flight Stress Blood Pressure Adrenal cortex - Mineralocorticoid = aldosterone DCT from renal tubule - promote sodium reabsorption Not enough" Addison disease CRH  ACTH Glucocorticoid = cortisone Many cells Mobilize fuels – stress adaptation Excess hormone: Cushing syndrome GnRH  GN Estrogen Testosterone Sexual organs - Sex organ maintenance - Gamete development Infertility
  • 90.
  • 91.
    91 Pancreas • Located adjacentto the stomach and is connected to the duodenum by the pancreatic duct. – Secretes bicarbonate ions and a variety of digestive enzymes into small intestine.  β cells of islets of Langerhans secrete insulin, and α cells secrete glucagon.  antagonistic  Insulin lowers while glucogen raises blood glucose.
  • 92.
    92 PANCREAS Duodenum Exocrine acini digestive enzymes Lobule } Endocrineislet metabolic hormones Ducts alkaline ions Enteroendocrine cells hormones
  • 93.
    93 Islet of Langerhans ISLET:Cell types & products Beta cell - insulin (majority) Alpha cell - Glucagon Delta cell - Somatostatin PP cell - Pancreatic polypeptide Beta & Alpha cells are directly sensitive to glucose level
  • 94.
    94 Antagonistic Actions ofInsulin and Glucagon
  • 95.
    95 Glucose regulation • Glucoselevel controlled by insulin and glucagon • Insulin promotes a decrease in blood glucose • Glucagon promotes an increase in blood glucose
  • 96.
  • 97.
  • 98.
    98 Diabetes mellitus • TypeI: autoimmune disease  beta cells of the islets of Langerhans are destroyed by antibodies • Type II: The cells become insulin-resistant  glucose does not enter the cells as readily
  • 99.
  • 100.
    100 Other Endocrine Glands •Ovaries and testes – produce androgen  secondary sexual characteristics • Pineal gland – secretes melatonin  regulates biological clocks
  • 101.
    101 Other Endocrine Glands •Molting and metamorphosis in insects – Hormone secretions influence both molting and metamorphosis in insects.  Brain hormone stimulates production of ecdysone (molting hormone).  high levels cause molting to occur  juvenile hormone  high levels prevent transformation to an adult
  • 102.
    102 Other Endocrine Glands •Endocrine disrupting chemicals – chemicals that interfere with hormone function  Any chemical that can bind to receptor proteins and mimic the effects of the hormone is called a hormone agonist.  Any chemical that binds to receptor proteins and has no effect, but blocks the hormone from binding is a hormone antagonist.
  • 103.
    103 Cerebral Cortex Cerebellum Pineal gland Brain Stem Eye& optic nerve Central sympathetic pathways Suprachiasmatic nucleus Thoracic cord Sympathetic preganglionic S Cervical ganglion Sympathetic postganglionics PINEAL ACTIVATION PATHWAY 1 3 4 2 5 7 Darkness increases HIOMT enzyme to make melatonin HydroxyIndole-O-MethylTransferase 1 7 6
  • 104.
    104 Cerebral Cortex Cerebellum Pineal gland BrainStem Eye & optic nerve Central sympathetic pathways Suprachiasmatic nucleus Thoracic cord Sympathetic preganglionic S Cervical ganglion Sympathetic postganglionics PINEAL ACTIVATION PATHWAY 1 3 4 2 5 6 1 7 7 melatonin light off Melanopsin in retinal ganglion cells is the photosensitive mediator
  • 105.
    105 Cerebral Cortex Cerebellum PINEAL GLAND BrainStem Eye & optic nerve Central sympathetic pathways Suprachiasmatic nucleus Thoracic cord Sympathetic preganglionic S Cervical ganglion Sympathetic postganglionics PINEAL ACTIVATION PATHWAY 1 3 4 2 5 7 Darkness increases HIOMT enzyme to make melatonin HydroxyIndole-O-MethylTransferase 6 melatonin light off
  • 106.
    106 cvlAl re uo - - -- - - - ENDOCRINE ORGANS II Plus neuroendocrine cells developed within mature gut, airway, etc epithelia [Kidney] [Heart] ANF EPO Renin VIP Gastrin Secretin, etc Gonads [Placenta] hCG Estrogen Progesterone Sex steroids [Adipose tissue] Leptin
  • 107.
    107 ATRIAL HEART &ANF Atrial myocytes have a well developed Golgi complex and secretory granules Reticular fiber Atrial Natriuretic Factor (ANF) in the granules STIMULATES: diuresis; sodium excretion (natriuresis); vasorelaxation; & INHIBITS the Renin-Angiotensin system & aldosterone secretion
  • 108.
    108 Enteroendocrine cell typesI Enteroendocrine cell small, pale, few; granules are located basally for release into the lamina propria Entero is misleading because: some cell types are confined to the stomach; and peptides & amines are signaling agents in other epithelia and other systems e.g. brain G cell - gastrin S cell - secretin I cell - cholecystokinin ECL cell - histamine D cell (antral) - somatostatin EC cell - serotonin A cell - ghrelin
  • 109.
    109 Enteroendocrine cell typesII Motilin cell: why not ‘M’ cell? There already is one, involved in immunity G cell - gastrin S cell - secretin I cell - cholecystokinin ECL cell - histamine L cell - glucagon-like peptide (GLP-1 & 2) peptide Y (PYY) oxyntomodulin K cell - gastric inhibitory polypeptide/GIP N cell - neurotensin M? cell - motilin D cell (antral) - somatostatin Coordinated with extrinsic & intrinsic neural controls and interacting amongst themselves EC cell - serotonin A cell - ghrelin
  • 110.
    110 EXOCRINE PANCREAS Controls Duodenum ExocrineaciniEnteroendocrine cells Secretin & CCK digestive enzymes HCO3 - ions RESPONSE Acid Fats Peptides STIMULI CONTROLLER + Vagal cholinergic control
  • 111.
    111 SOURCES OF ‘GUT’HORMONES RECTUM LIVER PANCREAS GALL BLADDER STOMACH SMALL GUT LARGE GUT Bile gastrin ghrelin Duodenum cholecystokinin motilin somatostatin neurotensin GIP-1 GLP-1&2 Peptide Y insulin glucagon PPY somatostatin secretin Oxyntomodulin
  • 112.
    112 SOURCES OF ‘GUT’HORMONES PANCREAS STOMACH SMALL GUT LARGE GUT gastrin ghrelin Duodenum cholecystokinin motilin somatostatin neurotensin GIP-1 GLP-1&2 Peptide Y insulin glucagon PPY somatostatin secretin Oxyntomodulin
  • 113.
    113 Enteroendocrine cell typesIII Immunostaining for the peptide or chromogranin and fluorescence methods for the amine derivatives now provide clear identification of the cells, but against a background of the old silver-based cell nomenclature A messy story*, because of the various staining reactions of enteroendocrine cells (particularly with silver methods) based on the peptide hormones, the associated chromogranin storage protein in the granules, and any catecholamine, serotonin or histamine content. ECL cell - EnteroChromaffin-Like cell
  • 114.
    114 Adipocyte hormones &other metabolic players RECTUM LARGE GUT LIVER SMALL GUT STOMACH PANCREAS GALL BLADDER E S O P H A G U S MOUTH APPENDI X SALIVARY GLAND AIRWAY HYPOTHALAMUS Appetites Homeostasis Emotion CEREBRAL CORTEX Cerebellum Pons Mid- brain Medulla PITUITARY TALUS CALCANEUS Metatarsa l FEMUR Fat cell Adipocytes MUSCLE
  • 115.
    115 Adipocyte hormones - LIVER HYPOTHALAMUS TALUS CALCANEUSMetatarsa l FEMUR Fat cell Adipocytes MUSCLE LEPTIN ADIPONECTIN for energy balance and glucose homeostasis
  • 116.
    116 Visceral/abdominal fat &type II diabetes, etc LIVER HYPOTHALAMUS TALUS CALCANEUS Metatarsa l FEMUR Fat cell Adipocytes MUSCLE LEPTIN ADIPONECTIN MACROPHAGES(MΦs) Macrophages accumulate in the stroma of the fatty tissue, become activated to release abnormal cytokines , e.g., TNF- α ,that disrupt many metabolic pathways so that the visceral adipose tissue is permanently inflamed and dangerous, e.g. Adipocyte production of adiponectin falls Insulin signalling goes bad, etc.
  • 117.
    117 TESTIS & LEYDIGCELLS Peritubular myoid cells LEYDIG INTERSTITIAL CELLS Acidophil Much smooth ER Lipid droplets Crystals of Reinke SERTOLI CELLS Sperm layered SPERMATOGENIC CELLS {stratified germinal epithelium BASAL LAMINA SEMINIFEROUS TUBULE SEMINIFEROUS TUBULE
  • 118.