Stimulated flow of pancreatic juice: called secretin
1905; Starling introduced the term Hormone
Greek: I arouse to activity or I excite
Definition of Hormone
Substance released by one cell to regulate another cell. Synonymous with chemical messenger. Delivered through endocrine, neuroendocrine, neurocrine, paracrine, autocrine systems.
Hormones can be:
Lipids (steroids, prostaglandins)
Proteins (FSH, TSH, GH)
Amino Acids (catecholamines)
Principal functions of the endocrine system
Maintenance of the internal environment in the body (maintaining the optimum biochemical environment).
Integration and regulation of growth and development.
Control, maintenance and instigation of sexual reproduction, including gametogenesis, coitus, fertilization, fetal growth and development and nourishment of the newborn.
Helps to maintain homeostasis by Integration & control.
Secretion of chemical signals called hormones that travel through the bloodstream to act on target cells.
Endocrine vs Nervous system Nervous system performs short term crisis management Endocrine system regulates long term ongoing metabolic
Types of cell-to-cell signaling Classic endocrine hormones travel via bloodstream to target cells; neurohormones are released via synapses and travel via the bloostream; paracrine hormones act on adjacent cells and autocrine hormones are released and act on the cell that secreted them.
Response vs. distance traveled
Endocrine action : the hormone is distributed in blood and binds to distant target cells. Paracrine action : the hormone acts locally by diffusing from its source to target cells in the neighborhood. Autocrine action : the hormone acts on the same cell that produced it.
Endocrine System: Overview
Endocrine system – the body’s second great controlling system which influences metabolic activities of cells by means of hormones.
A ductless gland composed of epithelial cells that releases secretions directly into extracellular fluid.
From the ECF the hormone diffuses into the bloodstream.
Pituitary, thyroid, parathyroid, adrenal, pineal, and thymus glands
The pancreas and gonads produce both hormones and exocrine products
The hypothalamus has both neural functions and releases hormones
Other tissues and organs that produce hormones – adipose cells, pockets of cells in the walls of the small intestine, stomach, kidneys, and heart
The Endocrine System
Types of Hormones
Proteins and Polypeptides- Hormones from anterior and posterior pituitary , Pancreas, Parathyroid gland. These hormones are stored in secretory vesicles until needed .Usually released into blood stream via exocytosis .
Steroid hormones : Hormones from adrenal cortex , ovaries and placenta .These hormones are usually synthesized from cholesterol and are not stored .
Amine hormones : Thyroid and adrenal medullary hormones .They are derived from Tyrosine .
A Structural Classification of Hormones
Protein and Polypeptide Hormones: Synthesis and Release
In some cases the prohormone is secreted and converted in the extracellular fluid into the active hormone: an example is angiotensin is secreted by liver and converted into active form by enzymes secreted by kidney and lung
There are two groups of hormones derived from the amino acid tyrosine
Thyroid hormones and Catecholamines
Thyroid hormones are basically a "double" tyrosine with the critical incorporation of 3 or 4 iodine atoms.
Thyroid hormone is produced by the thyroid gland and is lipid soluble
Thyroid hormones are produced by modification of a tyrosine residue contained in thyroglobulin, post-translationally modified to bind iodine, then proteolytically cleaved and released as T4 and T3. T3 and T4 then bind to thyroxin binding globulin for transport in the blood
Catecholamines are both neurohormones and neurotransmitters.
These include epinephrine, and norepinephrine
Epinephrine and norepinephrine are produced by the adrenal medulla both are water soluble
Secreted like peptide hormones
Synthesis of catecholamines
Two other amino acids are used for synthesis of hormones:
Tryptophan is the precursor to serotonin and the pineal hormone melatonin
Glutamic acid is converted to histamine
All steroid hormones are derived from cholesterol and differ only in the ring structure and side chains attached to it.
All steroid hormones are lipid soluble
Types of steroid hormones
Glucocorticoids ; cortisol is the major representative in most mammals
Mineralocorticoids ; aldosterone being most prominent
Androgens such as testosterone
Estrogens , including estradiol and estrone
Progestogens (also known a progestins) such as progesterone
Are not packaged, but synthesized and immediately released
Are all derived from the same parent compound: Cholesterol
Enzymes which produce steroid hormones from cholesterol are located in mitochondria and smooth ER
Steroids are lipid soluble and thus are freely permeable to membranes so are not stored in cells
Steroid hormones are not water soluble so have to be carried in the blood complexed to specific binding globulins.
Corticosteroid binding globulin carries cortisol
Sex steroid binding globulin carries testosterone and estradiol
In some cases a steroid is secreted by one cell and is converted to the active steroid by the target cell: an example is androgen which secreted by the gonad and converted into estrogen in the brain
1,25-dihydroxy Vitamin D3 is also derived from cholesterol and is lipid soluble
Not really a “vitamin” as it can be synthesized de novo
Acts as a true hormone
1,25-Dihydroxy Vitamin D3
Hormones and their receptors Hormone Class of hormone Location Amine (epinephrine) Water-soluble Cell surface Amine (thyroid hormone) Lipid soluble Intracellular Peptide/protein Water soluble Cell surface Steroids and Vitamin D Lipid Soluble Intracellular
A cell is a target because is has a specific receptor for the hormone Most hormones circulate in blood, coming into contact with essentially all cells. However, a given hormone usually affects only a limited number of cells, which are called target cells . A target cell responds to a hormone because it bears receptors for the hormone.
Hormones can be
Rapidly removed from bloodstream
Bound to transport proteins
Receptors for catecholamines, peptide hormones, eicosanoids are in the cell membranes of target cells.
Thyroid and steroid hormones cross the membrane and bind to receptors in the cytoplasm or nucleus.
Mechanisms of hormone action
Types of receptors
G Proteins and Hormone Activity
Special kind of Receptor
In plasma membrance .
Receptor for insulin and growth factors.
Adds phosphate to amino acid tyrosine
Tyrosine Kinase ( continued )
Hormone Effects on Gene Activity
Control of Endocrine Activity
The concentration of hormone as seen by target cells is determined by three factors:
Rate of production
Rate of delivery
Rate of degradation and elimination
Control of Hormone Synthesis and Release
Blood levels of hormones:
Are controlled by negative feedback systems
Vary only within a narrow desirable range
Hormones are synthesized and released in response to:
Humoral stimuli – secretion of hormones in direct response to changing blood levels of ions and nutrients
Example: concentration of calcium ions in the blood
Declining blood Ca 2+ concentration stimulates the parathyroid glands to secrete PTH (parathyroid hormone)
PTH causes Ca 2+ concentrations to rise and the stimulus is removed
Preganglionic sympathetic nervous system (SNS) fibers stimulate the adrenal medulla to secrete catecholamines
Hormonal stimuli – release of hormones in response to hormones produced by other endocrine organs
The hypothalamic hormones stimulate the anterior pituitary
In turn, pituitary hormones stimulate targets to secrete still more hormones
Nervous System Modulation
The nervous system modifies the stimulation of endocrine glands and their negative feedback mechanisms
The nervous system can override normal endocrine controls
For example, control of blood glucose levels
Normally the endocrine system maintains blood glucose
Under stress, the body needs more glucose
The hypothalamus and the sympathetic nervous system are activated to supply ample glucose
Feedback control of hormone secretion
Negative feedback :Prevents over secretion of the hormone or over activity at the target tissue .
Positive feedback :There are two or more variables ,if one increases the second one ,the second one in turn increases the first one or the 3rd one .E.g. Ovulation .
Cyclical Variations occur in hormone release
Feedback Control of Hormone Production Feedback loops are used extensively to regulate secretion of hormones in the hypothalamic-pituitary axis. An important example of a negative feedback loop is seen in control of thyroid hormone secretion
Negative feedback effects of cortisol
Glucose and insulin: as glucose increases it stimulates the pancreas to secrete insulin
Feedback control of insulin by glucose concentrations
Circadian (chronotropic) control
Regulates the activity of the nervous and endocrine systems
Highest level of endocrine control 1)Secrets regulatory hormones that control the anterior pituitary gland
2) Releases hormones at the posterior pituitary gland
3) Exerts direct neural control over the endocrine cells of the adrenal medullae.
Located at the basal part of the diencephalon lying below the thalamus
Split into left & right halves by the 3 rd ventricle
Has many neuroendocrine, behavioural and autonomic functions. Sexually dimorphic.
Sexual and ingestive behaviours
Control of body temperature
Integration of the cardiovascular & hormonal responses to stress
Within the hypothalamus there are many clusters of neurons hypothalamic nuclei
Two parts of the pituitary are anatomically are functionally DIFFERENT.
Derives from an inward invagination of the oral ectoderm of the primitive mouth cavity known as Rathke’s pouch
Arises from the neural ectoderm of the floor of the forebrain
Contains a variety of cell types which secrete hormones
Contains no secretory cell bodies which synthesize hormones
Composed of terminals of axons that originate in the hypothalamus
Cell body of neuron secretes hormone which travels down to the end of the axon
Posterior pituitary is ALL neural
Anterior pituitary (adenohypophysis)
1. Luteinizing hormone (LH)
2. Follicle Stimulating Hormone (FSH)
3. Thyroid Stimulating Hormone (TSH)
4. Growth Hormone (Somatotropin; GH)
5. Adrenocorticotropic Hormone (ACTH)
6. Prolactin (Prl)
Posterior pituitary (neurohypophysis)
Vasopressin (Antidiuretic Hormone; ADH)
Melanocyte Stimulating Hormone (MSH)
Anterior Pituitary Control
Hypothalamic control of anterior pituitary is very different than for the posterior pituitary
AP is regulated by chemical factors or hormones produced in the hypothalamus
Each anterior pituitary hormone probably has dual hypothalamic hormones - one inhibits and one stimulates
AP-regulating hormones travel from the hypothalamus to the anterior lobe by a specialized vascular route
Hypothalamic-pituitary portal system
The specialized vascular route is termed the hypothalamic-pituitary portal system
Portal system = two beds of capillaries connected by straight vessels
Figure 5.2.13 Feedback loops in a typical hypothalamo-hypophyseal axis. The target cell types (shaded area) may be any of those present in the anterior pituitary. They operate in a closed-loop feedback mode to maintain relatively steady plasma levels of the hormones concerned, subject to modifications of the hypothalamic drive by inputs from outside the body (exteroceptive signals), or intrinsic to the brain (pulse-generator). Long-loop and short-loop negative feedbacks involve respectively, the peripheral hormones and the tropic hormones.
Anterior pituitary hormones: Function
ACTH and TSH stimulate other endocrine gland
ACTH regulates the function of the adrenal cortex; increases release of adrenal steroids
TSH regulates the function of the thyroid gland; increases release of thyroid hormones
Pituitary Hormone Actions:
FSH (secreted by gonadotrope cells)
ovaries, stimulates development of eggs and follicles
testes, stimulates production of sperm
LH (secreted by gonadotrope cells)
females, stimulates ovulation and corpus luteum to secrete progesterone and estrogen
males, stimulates interstitial cells of testes to secrete testosterone
One hypothalamic factor (gonadotropin-releasing hormone – GnRH - decapeptide) stimulates the secretion of both hormones
Anterior pituitary hormones: Function of prolactin
Prolactin is the major hormone responsible for milk production (lactogenesis) and also is part of the hormone complex that promotes growth/development of the mammary glands (mammogenesis).
Blood levels of prolactin are low in non-pregnant, non-lactating females and in males.
However, during pregnancy and lactation, blood levels of prolactin increase, consistent with the hormone's role in mammary gland development and lactogenesis.
Essentially a hormone of reproduction.
Male, LH sensitivity in testes, thus testosterone secretion (gonadotropic effect in males)
Control of prolactin
Prolactin secretion regulation
Stimuli which increase is :
After2 to 3 hours of onset of sleep and continues through out the sleep
Exercise and stress
Nursing and breast stimulation
Dopamine antagonist like phenothiazine
Stimuli which decrease is :
Prolactin inhibitory factor (Dopamine)
Dopamine agonists: bromocriptine.
Maintenance of Lactation: Galactopoiesis
Hormonal control & milk removal
Prolactin along with growth hormone, glucocorticoids ,parathyroid hormone, and Insulin .
Prolactin (PRL): Disorders
Hypersecretion due to adenohypophyseal tumors; Common type of pituitary tumour (accounts for 60% of pituitary tumours). Other causes are due to primary hypothyroidism . The effects are due to associated decreased in FSH and LH levels
Results in galactorrhea (inappropriate milk production), lack of menses and infertility in women; impotence in men.
Treatment: Dopamine agonist: Bromocriptine .
Surgical removal of tumour .
Anterior pituitary hormones: Function of Growth Hormone
GH is important to growth and the control of metabolic functions
It acts directly on target cells which contain GH receptors
And as importantly, indirectly via the secondary generation of growth factors (peptides) called somatomedins in the liver.
There are at least two somatomedins (A and C. Somatomedins are also called insulin-like growth factors (IGF-1 and -2)
Metabolic Action of GH
Control of GH secretion
Growth Hormone Regulation
Growth hormone releasing hormone ,Hypoglycemia, Decrease in blood free fatty acids,Fasting,Exercise,Stress,Estrogens,Androgens, deep sleep.
Dwarfism : decreased secretion of hormone (prolonged steroid use) or decreased number of receptors (African pigmies)
Gigantism : excess secretion occurs during aldolescence before epiphyseal plates close. up to 8’ tall, normal body proportions
Acromegaly : excess secretion occurs during adulthood after epiphyseal plates close. Enlargement of extremities (hands and feet) and face, thickening of soft tissue.
Other Hormones Affecting Growth:
enhance GH effects and IGF production
tissue sensitivity to GH
aa uptake into muscle and protein synthesis in bone matrix formation;
GH/IGF receptors; IGF synthesis; vitamin D production
Gonadal Steroids: (cause epiphyseal closure)
Androgens - anabolic effects on muscle; GH secretion
Estrogens - mechanism unclear
osteoporosis in E 2 deficiency
Hormones (ADH, oxytocin) synthesized in hypothalamus
Travel down axons, stored in posterior pituitary
Released in response to increase frequency of action potentials in same axons
Whole system is nervous – cell bodies of neuron are in hypothalamus, axons terminate in posterior pituitary.
Actions of ADH: Water retention
ADH (vasopressin) has two actions, one on the kidney and the other on vascular smooth muscle. These actions are mediated by different receptors, different intracellular mechanisms, and different second messengers.
ADH: Increase in water permeability .
The major action of ADH is to increase the water permeability of cells in the kidney distal tubule and collecting duct .
The receptor for ADH on kidney cells is a V2 receptor, which is coupled to adenylyl cyclase via a Gs protein.
The second messenger is cAMP, which, via phosphorylation steps, directs the insertion of water channels, aquaporin 2, into the kidney cell membranes.
The increased water permeability of the cells allows more water to be reabsorbed by the collecting ducts (ie water moves from urine to blood) and makes the urine MORE concentrated or hyperosmotic.
ADH and contraction of vascular smooth muscle
The second action of ADH is to cause contraction of vascular smooth muscle (as implied by its other name, vasopressin).
The receptor for ADH on vascular smooth muscle is a V1 receptor, which is coupled to phospholipase C via a G protein.
The second messenger for this action is an IP2/Ca cascade which produces contraction of vascular smooth muscle, constriction of arterioles, and increased total peripheral resistance.
Figure 5.2.10 Summary of the pathways involved in control of ADH secretion.
Factor affecting ADH secretion
Hyposecretion due to damage of hypothalamic nucleus or neurohypophysis diabetes insipidus - excessive urine production (polyuria) and thirst
Hypersecretion SIADH (syndrome of inappropriate ADH secretion)
water retention, cerebral edema, headache, weight gain, hypo-osmolarity
Central (lack of ADH secretion): Head injury or tumour
Nephrogenic (renal tubule insensitivity to ADH)
Polyuria (excessive watery urine) followed by polydypsia ; thirst
Treatment :Analogues of ADH:Desmopressin (Nasal Spray)
Tumour: surgical removal of tumour
Actions of Oxytocin: Milk letdown
Milk ejection . Prolactin stimulates lactogenesis. The milk is stored in mammary alveoli and small milk ducts.
The major action of oxytocin is to cause milk letdown. When oxytocin is secreted in response to suckling or to conditioned responses, it causes contraction of myoepithelial cells lining these small ducts, forcing the milk into large ducts. The milk collects in cisterns and then flows out under pressure through the teat