Endocrine System

1. Anatomy and Physiology Endocrine System

2. General Characteristics of the Endocrine System • The endocrine system is so named because the cells, tissues, and organs that comprise it secrete substances into the internal environment. • The secreted substances, called hormones, diffuse from the interstitial fluid into the bloodstream and eventually act on cells, called target cells, some distance away.

3. Hormones and Endocrine Secretion • Hormones are proteins or lipids which can stimulate target cells even at very low concentrations. • They help regulate metabolic processes and homeostasis. • Paracrine secretions are not hormones but function in similar fashion. • Paracrine secretions enter the interstitial fluid but affect only neighboring cells. • Autocrine secretions affect only the secreting cell. • Exocrine secretion releases substances into ducts or a tube that is connected to the outside environment.

5. Chemistry of Hormones • Most hormones are either steroids that are synthesized from cholesterol or they are nonsteroids or glycoproteins that are synthesized from amino acids. • Hormones are organic compounds.

6. Steroid or Steroidlike Hormones

7. Hormones that contain nitrogens are the amine, peptide, protein, and glycoprotein hormones. Note the amino group: -NH 2 Nonsteroid Hormones

8. Protein Hormone—Amino Acid Sequence

9. Peptide Hormone: Amino Acid Seuqence

10. Prostaglandins • Prostaglandins are lipid hormones: paracrine substances derived from the fatty acid arachidonic acid, a polyunsaturated fatty acid • Hormones can stimulate target cells even at very low concentrations

11. Prostaglandin Structure

12. Prostaglandins • Paracrine Secretion: Hormones are secreted locally, such as into areas of inflammation. • Prostaglandins are lipids: • Local acting paracrine substances • Synthesized and released quickly and inactivated quickly • Can activate or inactivate adenylate cyclase • Can relax or contract smooth muscle • Stimulate hormone secretion • Influence sodium ion movement • Affect inflammation

13. Hormone Action • Hormones reach all cells but bind only those that have specific receptors. • Hormone receptors are a group of proteins or glycoproteins that have a specific hormone binding site. • A hormone then binds to its specific receptor forming a hormone-receptor complex . • The more specific receptors the corresponding hormone binds, the greater the response.

14. Steroid Hormones • Soluble in lipid environments such as in a cell membrane which is a phospholipid bilayer. • Easily diffuse into a cell . • Combine with specific protein receptors . • In the nucleus, the hormone-receptor complex binds to a specific region of DNA and activates genes which are then transcribed into mRNA . • The mRNA directs synthesis of a particular protein on the ribosome ( translation of mRNA into a protein ) which is located in the cytoplasm. • These proteins often are regulatory proteins which control metabolism and bring about cellular changes.

15. Steroid Hormone Action

16. Nonsteroid Hormones • Amine, peptide, and protein hormones combine with receptors that are located on the surface of the on the target cell membrane . • They bind at specific receptor binding sites which activates the receptor . • The activity site of the receptor interacts with other membrane proteins that reach across the phospholipid bilayer. • Receptor binding can trigger a cascade of biochemical reactions leading to the synthesis of a second messenger such as cyclic AMP.

17. Conversion of ATP into Cyclic AMP

18. Messengers • The hormone is the first messenger . • Cyclic AMP is a second messenger . • Hormone-receptor complex activates a G protein which activates adenylate cyclase which converts ATP to cAMP. • cAMP activates protein kinases • Protein kinases are enzymes that transfer phosphate groups from ATP to proteins and thereby activates them. • These proteins often are regulatory proteins which control metabolism and bring about cellular changes. • Phosphodiesterase deactivates cAMP

19. Second Messengers • Hormones whose actions depend upon cAMP • include: • TSH, ACTH, FSH, LH, ADH, PTH, epinephrine, norepinephrine, calcitonin, and glucagon and insulin. • Other second messengers: • cGMP, diacylglycerol, and inositol phosphate (releases calcium ions which combine with calmodulin).

20. Nonsteroid Hormone Action

21. Control of Hormone Secretion

22. Hypothalamus and Pituitary • Initially, the nervous system can stimulate glands. However, glands can also be stimulated or inhibited by the action of other hormones. • The hypothalamus controls the anterior pituitary through release of tropic hormones. Hypophyseal portal veins carry the hormones of the hypothalamus from the hypothalamus to the pituitary. • Two portions: • anterior lobe (adenohypophysis): • releases: TSH, GH, ACTH, FSH, LH, PRL; • Their secretion is affected by hypothalamic releasing hormones • posterior lobe (neurohypophysis): • does not produce hormones , but secretes hormones synthesized in neurosecretory cell • bodies in the hypothalamus

23. Negative Feedback System

24. Hormones of the Hypothalamus

25. Anterior Pituitary: Growth Hormone (GH) • Stimulates increase in size and mitotic rate of body cells, increases fat utilization • Hypothalamic growth hormone releasing hormone (GHRH) stimulates secretion; Somatostatin (SS) inhibits secretion • Enhances amino acid movement through membranes and promotes protein synthesis • Promotes long bone growth

26. Prolactin (PRL) • Sustains milk production after birth • Secretion stimulated by hypothalamic prolactin-releasing hormone (PRH) and inhibited by prolactin-inhibiting hormone (PIH) • Aids in decreasing LH secretion in men

27. Thyroid-Stimulating Hormone (TSH) = Thyrotropin • Controls secretion of hormones from the thyroid gland • Thyrotropin-releasing hormone (TRH) from the hypothalamus stimulates secretion • High levels lead to goiter

28. Adrenocorticotropic Hormone (ACTH) • Controls secretion of hormones from the adrenal cortex • Corticotropin-releasing hormone (CRH) from the hypothalamus stimulates secretion • Stress can stimulate CRH secretion

29. Follicle-stimulating Hormone (FSH) • A glycoprotein called also a gonadotropin • Gonadotropin-releasing hormone ( GnRH ) from the hypothalamus stimulates its secretion • In women , it stimulates the development of ovarian follicles, stimulates follicular cells to secrete estrogen • In men , this gonadotropin stimulates growth of the seminiferous tubules and sperm production

30. Luteinizing Hormone (LH) • Female gonadotropin LH or male gonadotropin LH = ICSH • Hypothalamic gonadotropin-releasing hormone ( GnRH ) stimulates its secretion • Promotes secretion of sex hormones ( testosterone ) • In women, it promotes egg release = ovulation

31. Posterior Pituitary: Antidiuretic Hormone (ADH) • Causes kidneys to retain water = concentrates urine • In high concentration, it raises blood pressure • Hypothalamus produces and posterior pituitary neurosecretory cells release ADH in response to changes in blood volume and changing blood concentration

32. Oxytocin (OT) • Contracts muscles in uterine wall and those associated with milk-secreting glands • Produced by the hypothalamus and secreted by neurosecretory cells in the posterior pituitary in response to uterine and vaginal wall stretching and stimulation of breasts

33. Thyroid Gland

34. Thyroid Gland • Follicles are filled with colloid composed mainly of thyroglobulin • Extrafollicular cells (C cells) lie outside the follicles • Three hormones: thyroxine (T4), triiodothyronine (T3), calcitonin • Affect cellular metabolic rates • Regulate metabolism of carbohydrates, lipids, and proteins

35. Structures of the Thyroid Hormones

36. Thyroxine and Triiodothyronine • Thyroxine (T4); Triiodothyronine (T3) • Regulate metabolism of carbohydrates, lipids, and proteins • Essential for growth and development and maturation of the nervous system • Iodine needed as integral part of molecules • Follicular cells secrete the precursor toT3/T4 which is without iodine (I) called thyroglobulin; upon addition of I, thyroglobulin becomes either T3 or T4 which are released into the blood

37. Calcitonin • Lowers blood calcium levels and phosphate ion concentration; high blood calcium • concentration stimulates secretion • Effect on bone matrix: Increases calcium and phosphate deposition • Effect on kidneys: Increases excretion of calcium and phosphate ions

38. Posterior View of Thyroid Gland Note: The trachea are anterior to the esophagus !!!

39. Parathyroid Hormone (PTH) • Stimulates bone resorption by osteoclasts and osteocytes • Inhibits activity of osteoblasts • Effect on kidneys: Causes kidneys to conserve calcium and excrete phosphate • Effect on intestine: Stimulates calcium absorption through vitamin D Low blood calcium concentrations stimulate secretion of PTH from the parathyroid gland • Four small glands found on the posterior surface of the thyroid gland Secrete parathyroid hormone ( PTH ) or parathormone, a protein hormone • PTH increases blood calcium concentration and phosphate concentration by bone resorption • Parathyroid Gland

40. Cholesterol and PTH

42. Adrenal Gland and Kidney • The adrenal gland cortex secretes the corticoids by endocrine secretion: mineralocorticoids (aldosterone), glucocorticoids (cortisol), and steroidal corticoids (testosterone/estrogen precursors). • The medulla secretes: catecholamines (norepinephrine, epinephrine). • The kidney secretes: renin and erythropoetin.

43. Adrenal Gland • An endocrine gland located in the abdomen superior to the kidney. • Under conditions of fear or stress, a surge of the hormone adrenaline mobilizes the body for peak physical response. • Flooding the bloodstream at up to 300 times the normal concentration, the adrenaline interacts with receptors on cells in various organs, increasing the heart rate and blood pressure and prompting the release from the liver of extra sugar to fuel muscular work. • Taken together, these reactions constitute a “Fight or flight” response .

44. Adrenal Gland • In the medulla, specialized cells known as chromaffin cells manufacture, store, and secrete a complex mixture of hormones, the most important of which is adrenaline . • The adrenal medulla can also be thought of, however, as part of the sympathetic nervous system , which helps to regulate such involuntary functions as heart rate, intestinal movements and the dilation of the pupil. • The adrenal medulla is controlled by nerves originating in the spinal cord; its primary hormone, adrenaline , is closely related to noradrenaline, the characteristic neurotransmitter of the sympathetic nerves . • Moreover, the adrenal medulla itself secretes noradrenaline and neurologically active substances known as neuropeptides.

45. Secretion stimulated by angiotensin II, triggered by low plasma sodium levels Acts on the kidney to conserve sodium and excrete potassium Indirectly increases blood volume Mineralocorticoid form the zona glomerulosa: Aldosterone

46. Cortisol Cortisol Stimulates gluconeogenesis. However, it also: Inhibits protein synthesis, increasing blood concentration of amino acid Promotes fatty acid release; increases fatty acid use for energy and decreases use of glucose Glucocorticoid from the zona fasciculata

47. Steroidal corticoids from the zona reticularis: Sex Hormones • Adrenal androgens predominate (precursors to testosterone ) • Androgens can be converted to estrogens by the skin, liver, and adipose tissue. • All sex hormones have the basic 4D ring structure common to steroids.

48. Pancreas • Glucagon secreted by α cells (alpha cells) in the islets of Langerhans stimulates liver to break down glycogen and convert noncarbohydrate into glucose stimulates fat breakdown into fatty acids and glycerol increases blood glucose levels; secreted in response to low blood glucose

49. Pancreas • Insulin secreted by β cells (beta cells) of the Langerhans islets promotes facilitated diffusion of glucose into cells with insulin receptors (adipose, muscle) for the synthesis of glycogen stimulates adipose cells to store fat decreases blood glucose levels; secreted in response to high blood glucose • Somatostatin secreted by δ cells ( delta cells) of the islets of Langerhans similar to hypothalamic hormone inhibits secretion of glucagon and insulin

50. Pancreas