Introduction to Endocrine Physiology What is endocrine communication? Comparison of endocrine and neural mechanisms: Neural is nearly instantaneous on and off; endocrine is gradual on and off Neural is local – messenger goes straight to target cell. Endocrine is global – messenger is carried in circulation Endocrine glands = ductless (direct secretion into circulation) Subtypes: neuroendocrine cells/glands, neurohormones

General Principles Subject matter = actions of hormones and control of their secretion Generally, endocrine mechanisms control things over long term (growth and maturation, control of water and electrolyte balance, control of levels of circulating metabolites, reproduction, integration of activities over long periods Endocrine system is anatomically discontinuous, functions as a system. Tropic hormones mainly control secretion of other hormones. Nontropic hormones mostly affect cells outside the endocrine system Some endocrine glands produce more than one hormone, but one cell only secretes one hormone. Many hormones have effects on a number of kinds of cells, and nearly every cell is a target for more than one hormone. Most hormones have multiple effects, so “the action” of a hormone is an error, although common. Hormones act at remarkably low concentrations, by definition.

Classification of Hormones Three broad categories: Peptide Steroid “Amine” “Amine” is really just a category for any hormone that isn’t a peptide or a steroid. All “amine” hormones do contain an amino group, but so do all peptides Each category has a set of common characteristics, so the classification simplifies things. Peptide hormones have common mechanisms of synthesis, storage, secretion, transport in plasma and actions on target cells. The same is true of steroid hormones.

Peptide Hormones Small proteins that are exported from the cell that produces them. Synthesized on ribosomes (like all proteins) as inactive precursors. Migrate through endoplasmic reticulum (ER) to Golgi zone; packaged into vesicles and converted to active forms in ER or Golgi zone. Secreted by exocytosis. Water-soluble, circulate as simple dissolved compounds. Too big to enter cells, bind to receptors on surface of target cells. This initiates response: direct effect on membrane channels or, more often release of “second messenger” (usually Ca or cAMP) into cytoplasm. Second messenger causes metabolic response by target cell. Peptides are digested in stomach, so they’re unsuited for oral administration.

Steroid Hormones Most significant difference between peptides and steroids is that peptides are water soluble, steroids are lipid soluble. Because of lipid solubility, steroid hormones cross membranes. They can’t be stored, are secreted as synthesized. Enter target cells and act intracellularly instead of binding to receptors on target cell membranes. Most act in the cell nucleus, directly on target cell DNA. Steroids are bound to specific proteins in plasma. Target cells have surface components that cause release of bound steroids from those proteins. Steroids are not digested in the gut, and are readily absorbable. Thus, many can be administered orally.

“Amine” Hormones All are derivatives of tyrosine, and all can be stored prior to secretion. Otherwise, there’s no easy generalizations that apply to the group.

Control of Circulating Hormone Levels Any change in circulating level of a hormone must be due to a change in rate of secretion (the only input) or rate of removal from the circulation (taken up by target cells, destroyed metabolically, or excreted in kidneys), or both. The factor that is under physiological control is rate of secretion, via a negative feedback loop between plasma concentration of the hormone and rate of secretion. This is nearly universal.

Endocrine Disorders Pathologically high plasma levels of hormone - hypersecretion Pathologically low plasma levels of hormone - hyposecretion Abnormal responses by target cells

Abnormal Responses and Down Regulation When hormone binds to surface receptor, hormone-receptor complex is taken into cell by endocytosis. Hormone and receptor are hydrolyzed in lysosomes, terminating stimulation. New receptors are synthesized and inserted into membrane. Since receptor synthesis is often slower than receptor digestion, high levels of hormone can result in decreased numbers of receptors. Decreased numbers of receptors cause decreased responses to hormone. This is known as down regulation.

Basic Anatomy of the Pituitary Gland (= Hypophysis) Connecting stalk = infundibulum Anterior lobe (= adenohypophysis) is glandular epithelial, budded off roof of mouth. Connected to hypothalamus by vasculature (= hypothalamo-hypophyseal portal system). Posterior lobe (= neurohypophysis) is neural tissue, outpocket from brain. Connected to hypothalamus by vasculature and by nerves.

Intermediate Lobe and MSH There’s a third lobe in most animals (not humans) that produces melanocyte stimulating hormone (MSH). MSH regulate melanin dispersion in skin cells, which darkens skin. Human anterior lobe produces MSH. High levels darken skin, but those levels only occur pathologically. It has nothing to do with skin color variations between races or skin darkening from sunlight.

Hypothalamus-Posterior Lobe Relations Hypothalamus is involved in control of secretion of anterior and posterior lobe hormones. Supraoptic and paraventricular nuclei have neurons with axons that project through the infundibulum, terminate in neurohypophysis

Most posterior lobe cells are pituicytes, don’t secrete. Supraoptic and paraventricular nuclei -> two peptide hormones each, secreted from axon terminals in the posterior lobe. 1.Vasopressin = ADH 2.Oxytocin Synthesized in hypothalamus, packaged into vesicles that migrate down axons, are stored in axon terminals.

Posterior Lobe Hormones Both are neurohormones. You already know about ADH. It’s also a not-very-powerful vasoconstrictor, which is why it’s also called vasopressin. Major stimulus to secretion is increased plasma osmolarity, cells that secrete it are osmoreceptors. Oxytocin: major effect is promotion of uterine contraction during childbirth and ejection of milk from breasts. Major stimuli to secretion are reflexes originating from stretch receptors in cervix and vagina, and mechanical stimulation of nipples.

Anterior Lobe Hormones Synthesized in and secreted from adenohypophysis, all are peptides. The six anterior lobe hormones are: 1.Growth hormone = somatotropin = GH 2.Prolactin = Prl 3.Thyroid stimulating hormone = thyrotropin = TSH 4.Adrenocorticotropic hormone = adrenocorticotropin = ACTH 5.Follicle stimulating hormone = FSH 6.Luteinizing hormone = LH = Interstitial Cell Stimulating hormone = ICSH GH and Prl are (for us, at least), nontropic. TSH, ACTH, FSH and LH are all tropic. FSH and LH are tropic to secretions by the gonads, so they are called gonadotropins.

Control of Secretion of Anterior Lobe Hormones Two major kinds of control: 1.Negative feedback from hormones released by target organs of tropic hormones (long loop). 2.Tropic hormones produced and secreted by hypothalamus (short loop) Blood supply to anterior pituitary has already been in hypothalamic capillaries (hypothalamo-hypophyseal portal system), so hypothalamic hormones reach anterior lobe without dilution by general circulation. Secretion of all six anterior lobe hormones is modulated by hypothalamic hormones. With one exception, the hypothalamic hormones are peptides. All are neurohormones, all are tropic.

Hypothalamic Hormones Thyrotropin releasing hormone = TRH Corticotropin releasing hormone = CRH Gonadotropin releasing hormone = GnRH Prolactin releasing hormone = PRH Prolactin inhibiting hormone = PIH (catecholamine, not peptide) Growth hormone releasing hormone = GRH Growth hormone inhibiting hormone = GHIH Note that the two anterior lobe hormones not subject to negative feedback from hormones released by their targets are subject to inhibitory as well as stimulatory hypothalamic hormones. Secretion of TRH, CRH and GnRH are all subject to negative feedback inhibition by hormones of the thyroid, adrenal cortex and gonads, respectively.