ENDOCRINE SYSTEM Chapter Goals 1 describe the structure

ENDOCRINE SYSTEM: Chapter Goals 1. describe the structure of the pituitary gland explain the functional relationship between the pituitary and the hypothalamus. 2. list the hormones released by the posterior pituitary, state the origin of these hormones, and explain how the hypothalamus regulates their release. 3. list the hormones of the anterior pituitary and explain how their secretion is regulated by the hypothalamus. 4. describe the production and actions of the thyroid hormones and explain how thyroid secretion is regulated. 5. describe the location of the parathyroid glands and explain the actions of PTH and the regulation of its secretion. 6. describe the types and actions of corticosteroids and explain how the secretions of the adrenal cortex are regulated. 7. describe the actions of epinephrine and norepinephrine, and explain how the secretions of the adrenal medulla are regulated. 8. explain why the pancreas is both an exocrine and an endocrine gland describe the structure and functions of the pancreatic islets.

ENDOCRINE SYSTEM: Chapter Goals 9. describe the actions of insulin and glucagon, and explain the regulation of their secretion. 10. list the hormones secreted by the gonads and placenta.

ENDOCRINE SYSTEM • General Principles of Endocrinology • Central Endocrine Glands – Pineal Gland – Hypothalamus – Hypophysis cerebri (Pituitary) • Peripheral Endocrine Glands – – – Thyroid Parathyroids Adrenal Glands Pancreas Gonads

Principles of Endocrinology • Endocrine Glands - Glands of internal secretion (products are emptied directly into the circulation)

Hormones • 1. Definition - Chemical messengers (produced in one location and work somewhere else) • 2. Types • Peptides • Amines – Catecholamines (epinephrine, nor-epinephrine) – Thyroxine • Steroids

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Hormones • 3. Chemical Properties • Hydrophilic and Lipophobic – Peptides -- work via a second messenger, c. AMP Adenylate Cyclase ATP __________> 2', 3'-c. AMP – Catecholamines - via 2 nd messengers • Hydrophobic and Lipophilic – Thyroxine - Activates genes – Steroids -- activate genes

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Central Endocrine Glands • Pineal Gland • Hypothalamus • Hypophysis cerebri (Pituitary)

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Pineal Gland • Melatonin - regulates circadian rhythms (increases in dark) • May induce sleep • May initiate puberty • May inhibit ovulation/spermatogenesis • May be antioxidant • May slow aging • May enhance immunity

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Hypothalamic Hormones • Generalities • Regulators of Adenohypophysis • Neurohypohysis - hormones produced in hypothalamus

Generalities • If purified and structure is known = hormone • otherwise = factor. • Materials transported from hypothalamus to hypophysis by hypothalamic-hypophyseal portal system

Regulators of Adenohypophysis • if final target is another endocrine gland, production of hypothalamic hormone (hh) is regulated by negative feedback, so only one hh is required • otherwise, 2 hh are required: one to cause release and one to inhibit release of adenohypophyseal hormone.

Hypophysis cerebri • (= pituitary) - called the "master gland", because it regulates other glands. – Adenohypophysis (=anterior lobe) – Neurohypophysis (= Posterior Lobe)

Neurohypophysis (=posterior lobe) • oxytocin - stimulates smooth muscle contraction --> childbirth & milk release. • Antidiuretic hormone (ADH) (=vasopressin) --> increased permeability of collecting tubules to water

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Adenophpophysis • Growth Hormone (GH) (= somatotropin) - regulates growth. • Prolactin (= Luteotropic hormone, LTH) - stimulates milk production; no known role in males. • Adrenocorticotropic hormone (ACTH) (= corticotropin) stimulates adrenal cortex. • Thyroid Stimulating Hormone (TSH) (=Thyrotropin) Stimulates thyroid gland to secrete thyroxine • Gonadotropins (Act on gonads) – Follicle Stimulating Hormone (FSH) – Luteinizing Hormone (LH)

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Growth Hormone • Regulates growth • Overproduction in children ---> gigantism; in adults ---> acromegaly. Underproduction --> pituitary midget (perfect proportions). Available commercially via recombinant DNA technology.

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Peripheral Endocrine Glands • Thyroid Gland • Parathyroid Glands • Adrenal Glands • Pancreas

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Thyroid Gland • -->Thyroxine (tyrosine + 4 I; therefore low iodine --> goiter) - Regulates BMR • a. Hyperthyroidism --> high metabolic rate (extreme --> exophthalmos). Treated by propylthiouracil, thyroidectomy, or radioactive iodine. • b. Hypothyroidism --> cretinism in children & myxedema in adults

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Parathyroid Gland • (4 next to thyroid) --> parathyroid hormone (= parathormone). • a. Regulates free Calcium metabolism (99% of Ca++ in bones, 0. 5% bound to blood protein, 0. 5% free. • b. Controlled by Ca++, not pituitary • c. Role of p. H (e. g. low p. H --> increased Ca++ absorption and mobilization from bone, and decreased Ca++ excretion). • d. Role of Blood Ca++ – i. Too much Ca++ --> depressed neural and muscle function – ii. Too little Ca++ --> enhanced excitability of nerves and muscles.

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Adrenal Gland • a. Adrenal Medulla --> epinephrine & norepinephrine (A modified sympathetic postganglionic neuron) • b. Adrenal Cortex --> numerous steroids (3 major groups) • i. Mineralocorticoids (e. g. aldosterone - regulates Na+ & K+ in blood). • ii. Glucocorticoids (e. g. cortisone - causes: gluconeogenesis, mobilization of amino acids, mobilization of fats. Anti-inflammatory agent released in response to stress) • iii. Androgens - Normally have no effect

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Pancreas • Structure – i. Exocrine portion --> enzymes – ii. Endocrine portion = Islets of Langerhans • (a) Alpha-cells --> glucagon • (b) Beta-cells --> insulin • Function

Function (cont’d) insulin • Glucose < ---------------- >Glycogen glucagon • Too little insulin --> diabetes --> hyperglycemia (cells can't get glucose, so use fats --> keto acids (acetone breath) --> low blood p. H --> high free Ca++ -->depressed nerve and muscle function --> hyperglycemic shock. • Too much insulin --> hypoglycemia. Since brain can only use glucose for an energy source --> hypoglycemic shock (insulin coma).

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Gonads • Testes --> testosterone (Starts in fetus --> development of male sex organs & descent of testes. At puberty --> secondary male sexual characteristics. • Ovaries --> estrogens (e. g. 17 -beta-estradiol) & progesterone --> secondary female sexual characteristics. Also play a role in the reproductive cycle (details on board).

Chapter Summary Endocrine Glands and Hormones I. Hormones are chemicals that are secreted into the blood by endocrine glands. A. The chemical classes of hormones include amines, polypeptides, glycoproteins and steroids. B. Nonpolar hormones, which can pass through the cell membrane of their target cells, are called lipophilic hormones. II. Precursors of active hormones may be classified as either prohormones or prehormones. A. Prohormones are relatively inactive precursor molecules made in the endocrine cells. B. Prehormones are the normal secretions of an endocrine gland that in order to be active must be converted to other derivatives by target cells. III. Hormones can interact in permissive, synergistic, or antagonistic ways. IV. The effects of a hormone in the body depend on its concentration. A. Abnormally high amounts of a hormone can result in atypical effects. B. Target tissues can become desensitized by high hormone concentrations.

Chapter Summary Mechanisms of Hormone Action I. The lipophilic hormones (steroids and thyroid hormones) bind to nuclear receptor proteins, which function as ligand-dependant transcription factors. A. Some steroid hormones bind to cytoplasmic receptors, which then move into the nucleus. Other steroids and thyroxine bind to receptors already in the nucleus. B. Each receptor binds to both the hormone and to a region of DNA called a hormone-response element. C. Two units of the nuclear receptor are needed to bind to the hormone-response element to activate a gene; as a result, the gene is transcribed (makes m. RNA).

Chapter Summary Mechanisms of Hormone Action II. The polar hormones bind to receptors located on the outer surface of the cell membrane. This activates enzymes that enlist second-messenger molecules. A. Many hormones activate adenylate cyclase when they bind to their receptors. This enzyme produces cyclic AMP (c. AMP), which activates protein kinase enzymes within the cell cytoplasm. B. Other hormones may activate phospholipase C when they bind to their receptors. This leads to the release of inositol triphosphate (IP 3), which stimulates the endoplasmic reticulum to release Ca 2+ into the cytoplasm, activating calmodulin. C. The membrane receptors for insulin and various growth factors are tyrosine kinase enzymes that are activated by binding to the hormone. Once activated, the receptor kinase phosphorylates signaling molecules in the cytoplasm that can have many effects.

Chapter Summary Pituitary Gland I. The pituitary gland secretes eight hormones. A. The anterior pituitary secretes growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, follicle-stimulating hormone, luteinizing hormone, and prolactin. B. The posterior pituitary releases antidiuretic hormone (also called vasopressin) and oxytocin, both of which are produced in the hypothalamus and transported to the posterior pituitary by the hypothalamo-hypophyseal nerve tract. II. The release of posterior pituitary hormones is controlled by neuroendocrine reflexes. III. Secretions of the anterior pituitary are controlled by hypothalamic hormones that stimulate or inhibit these secretions. A. Hypothalamic hormones include TRH, CRH, Gn. RH, PIH, somatostatin, and a growth hormone-releasing-hormone. B. These hormones are carried to the anterior pituitary by the hypothalamohypophyseal portal system.

Chapter Summary Pituitary Gland IV. Secretions of the anterior pituitary are also regulated by the feedback (usually negative feedback) exerted by target gland hormones. V. Higher brain centers, acting through the hypothalamus, can influence pituitary secretion.

Chapter Summary Adrenal Glands I. The adrenal cortex secretes mineralocorticoids (mainly aldosterone), glucocorticoids (mainly cortisol), and sex steroids (primarily weak androgens). A. The glucocorticoids help to regulate energy balance. They also can inhibit inflammation and suppress immune function. B. The pituitary-adrenal axis is stimulated by stress as a part of the general adaptation syndrome. II. The adrenal medulla secretes epinephrine and lesser amounts of norepinephrine. These hormones complement the action of the sympathetic nervous system.

Chapter Summary Thyroid and Parathyroid Glands I. The thyroid follicles secrete tetraiodothyronine (T 4, or thyroxine) and lesser amounts of triiodothyronine (T 3). A. These hormones are formed within the colloid of the thyroid follicles. B. The parafollicular cells of the thyroid secrete the hormone calcitonin, which may act to lower blood calcium levels. II. The parathyroids are small structures embedded within the thyroid gland. They secrete a parathyroid hormone (PTH) which promotes a rise in blood calcium levels.

Chapter Summary Pancreas and Other Endocrine Glands I. Beta cells in the islets secrete insulin and alpha cells secrete glucagon. A. Insulin lowers blood glucose and stimulates the production of glycogen, fat, and protein. B. Glucagon raises blood glucose by stimulating the breakdown of liver glycogen. It also promotes lipolysis and the formation of ketone bodies. C. The secretion of insulin is stimulated by a rise in blood glucose following meals. The secretion of glucagon is stimulated by a fall in blood glucose during periods of fasting. II. The pineal gland, located on the roof of the third ventricle of the brain, secretes melatonin. A. Melatonin secretion is regulated by the suprachiasmatic nucleus of the hypothalamus, which is the major center for the control of circadian rhythms. B. Melatonin secretion is the highest at night, and this hormone has a sleep -promoting effect. In many species, it also has an antigonadotropic effect and may play a role in timing the onset of puberty in humans, although

Chapter Summary Pancreas and Other Endocrine Glands III. The thymus is the site of T cell lymphocyte production and secretes a number of hormones that may play a role in regulating the immune system. IV. The gastrointestinal tract secretes a number of hormones that help regulate digestive functions. V. The gonads secrete sex steroid hormones. A. Leydig cells in the interstitial tissue of the testes secrete testosterone and other androgens. B. Granulosa cells of the ovarian follicles secrete estrogen. C. The corpus luteum of the ovaries secretes progesterone, as well as estrogen. VI. The placenta secretes estrogen, progesterone, and a variety of polypeptide hormones that have actions similar to some anterior pituitary hormones.

Chapter Summary Autocrine and Paracrine Regulation I. Autocrine regulators are produced and act within the same tissue of an organ, whereas paracrine regulators are produced within one tissue and regulate a different tissue of the same organ. Both types are local regulators, they do not travel in the blood. . II. Prostaglandins are special, twenty-carbon-long fatty acids produced by many different organs. They usually have regulatory functions within the organ in which they are produced.