Endocrine Physiology andMechanisms of Hypothalamic- Pituitary Regulation Chapter 39
Endocrine System • Composed of cells and organs that are specialized to synthesize and secrete hormones into the bloodstream to act at distant target cells • Hormones are blood-borne chemical messengers that affect target cells anatomically distant from the secreting cell
How to go through the Endocrine System?• What is the gland?• What triggers it to secrete?• What is the secreted product (hormone)?• What is the target of the hormone?• What is the resulting work of the hormone?
THEN…..• Three things that make a gland secrete:1. Hormonal stimulation – Hormone to hormone • Hypothalamus pituitary • Pituitary thymus2. Humoral fluids – What ions/proteins in the fluids • Ca2+ levels, blood sugar3. The Nervous System – Sympathetic stimuli • Epinephrine and norepinephrine
Endocrine vs. Exocrine Glands Where do they secrete their products?
HORMONAL CONTROLWhat is negative feedback?• Occurs when there is a drop in the level of a hormone – triggers a chain reaction of responses to increase hormones in the blood – most hormones are regulated by negative feedback – OXYTOCIN: POSITIVE FEEDBACK
Where is the hormone going?• Only the target cells for a given hormone have receptors that bind and recognize that hormone.
Hormones• Neurocrine—secretion of hormones into the bloodstream by neurons• Endocrine—secretion of hormones into the bloodstream by endocrine glands• Paracrine—hormone molecule secreted by one cell affects adjacent cells• Autocrine—hormone molecule secreted by a cell affects the secreting cell
Hormones: Mechanism of action Hormones with Cell Membrane Receptors • Water-soluble hormones have a hormone-binding site located on the external portion of a specific cell-surface receptor • Hormones exert their action by binding to target cell receptor proteins • Once binding takes place, a conformation of the receptor protein conveys a signal to the interior of the cell • Amplification of the hormone activity is achieved by activation of a cascade of chemical reactions
Hormones: Mechanism of action Hormones with Cell Membrane Receptors Water Soluble Hormones
Hormones: Mechanism of action Hormones with Cell Membrane Receptors
Hormones: Mechanism of action Hormones with Intracellular Receptors • Lipid-soluble (thyroid and steroid) hormones diffuse easily through the lipid bilayer of cell membranes • Receptors for these hormones are located in the cytoplasm, or in the nucleus of the target cell • Binding causes a change in affinity of the receptor for binding sites on DNA in the cell nucleus • Gene expression is changed by binding of the hormone-receptor complex to specific DNA binding sites • Onset of action of lipid-soluble hormones is slow compared with water-soluble hormones and there is no amplification cascade
Hormones: Regulation Hormone Synthesis, Secretion, Metabolism • Most endocrine hormones are polypeptides manufactured on the rough endoplasmic reticulum and stored in vesicles within the cells • Cleaved by specific enzymes to release the active form of the hormone Enzyme Pre hormone Cleavage Hormone fragment
Hormones: Regulation Hormone Synthesis, Secretion, Metabolism • Water-soluble hormones – Peptide hormones: CONTAINED WITHIN LIPID BILAYER OF THE VESICLES and stored until a trigger results in exocytosis of the hormone into the extracellular space – Catecholamines: formed by enzymes within the cytoplasm that begin with tyrosine and through a series of steps convert it to dopamine, norepinephrine, or epinephrine
Hormones: Regulation Hormone Synthesis, Secretion, Metabolism • Lipid-soluble hormones – Steroid hormones: FORMED ON DEMAND from cholesterol that is stored in the cell or retrieved from the circulating lipoproteins – Thyroid hormones: synthesis precedes secretion by weeks or months in the thyroid follicle and bound to protein thyroglobulin; secretion occurs via cleavage of the thyroid hormone based on systemic needs determined by the hypothalamus and pituitary gland
Pituitary Gland Pituitary Gland (Hypophysis) • Located beneath the hypothalamus in the sella turcica • Connected to hypothalamus by the pituitary stalk • • Composed of anterior (adenohypophysis) and posterior (neurohypophysis) lobes
HORMONES OF THE PITUITARY GLAND• Divided into two lobes – anterior pituitary lobe is larger and produces SIX hormones; stimulated by releasing and inhibiting hormones from the hypothalamus; connected by hypophyseal portal veins – posterior pituitary lobe is smaller and consists primarily of axons whose cell bodies are in the hypothalamus
Sphenoid bone Portal veins deliver releasing & inhibiting hormones from hypothalamus. Pituitary Gland
Flow of Blood to Anterior Pituitary• Releasing & inhibiting hormones enter blood (hypothalamus)• Travel through portal veins• Enter anterior pituitary at capillaries• Hormones travel to destination
Hypothalamic Neurosecretory Cells•Does not synthesize hormones• Hormones packaged & travel by axons of hypothalamic neurons
Pituitary Gland • The hypothalamus regulates endocrine function of the ANTERIOR PITUITARY by SECRETING RELEASING AND INHIBITING HORMONES INTO THE PORTAL SYSTEM between the hypothalamus and pituitary that transports capillary blood from the hypothalamus to the capillaries of the anterior lobe • Release of POSTERIOR PITUITARY hormones occurs WHEN ACTION POTENTIALS GENERATED IN THE HYPOTHALAMIC NEURONS TRAVEL DOWN THE AXONS of the pituitary stalk and trigger exocytosis of hormone from the nerve terminals in the posterior pituitary gland
On each side of trachea is lobe of thyroid Butterfly-shaped gland; located in the anteriorThyroid Gland part of neck
Thyroid Gland • Main function of thyroid is production and secretion of metabolically active hormones that are essential for regulation of various metabolic processes. • Thyroid hormones are made from tyrosine and iodine.
THYROID– Secretes 3 hormones: • Thyroxine/ Tetraiodothyronine (T4) • Triiodthyronine (T3) • Calcitonin: Decreases the level of calcium in the blood & increases uptake of calcium into bone matrix
Thyroid Gland Most important thyroid hormones are: - Thyroxin (T4) - Triiodothyronine (T3) → Approximately 90% of the thyroid hormone is in the form of T4, whereas 10% is T3 Source: Clinical Chemistry. 2010. Kaplan and Pesce. Mosby.
Thyroid•Follicle = sac of stored hormone Makes thyroglobulinContains thyroglobulinwith attached iodinemolecules
Actions of Hormones from Thyroid Gland • T3 & T4 : thyroid hormones responsible for our metabolic rate, synthesis of protein, breakdown of fats, use of glucose for ATP production • Calcitonin: responsible for building of bone & stops reabsorption of bone by osteolasts (lowers blood levels of Calcium)
ADRENAL GLANDS• Two adrenal glands located on top of each kidney; each has two parts – Cortex • Mineralocorticoids • Glucocorticoids Regulation the three S’s Salt, sugar and sex • Androgens – Medulla • epinephrine • norepinephrine
Glucocorticoid: Cortisol• Glucose formation: gluconeogenesis (prime effect)• Breakdown of protein • (increase release of amino acids into blood stream)• Breakdown of fat (lipolysis)• Depression of Immune function • (Prescribed for organ transplants)• Anti-Inflammatory effects • (inhibit WBC’s but also retard tissue repair)• Resistance to stress: Provide tissues with a ready supply of ATP
Adrenal Gland: Cortisol Normally cortisol is present in the body at higher levels in the morning, and at its lowest at night.
Categories of Endocrine Disease• Hyposecretion• Hypersecretion• Target cell hyporesponsiveness
Categories of Endocrine Disease• Hyposecretion – Primary hyposecretion occurs when an ENDOCRINE GLAND releases an inadequate amount of hormone to meet physiologic needs – Secondary hyposecretion occurs when secretion of a TROPIC HORMONE is inadequate to cause the target gland to secrete adequate amounts of hormone
Categories of Endocrine Disease (Cont.)• Hypersecretion – Primary hypersecretion occurs when there is a DYSFUNCTION OF THE ENDOCRINE GLAND that results in abnormally high secretion of hormone – Secondary hypersecretion occurs when there is an ELEVATION IN THE TROPIC LEVEL of one hormone that results in an increased plasma concentration of the endocrine gland hormone also
Categories of Endocrine Disease• Target cell hyporesponsiveness – Typically due to lack of or a deficiency in cellular receptors, but can occur with postreceptor mechanisms, such as second-messenger dysfunction that causes decreased cellular response – Hormone resistance of the target tissues will cause the same set of clinical symptoms as hyposecretion