ADRENOCORTICAL HORMONE

1. ADRENOCORTICAL HORMONE Dr. AmelEassawi

2. Objectives At the end of this lecture the student should be able to • Enumerate the adrenocortical hormones. • Describe the chemical nature, source and actions of mineralocorticoid hormone. • Describe the chemical nature, source and actions of Glucocorticoid hormone. • Describe the chemical nature, source and actions of adrenal androgens hormone. • Describe the feed back control of adrenocortical hormones. • Describe the pathophysiology of hypo & hyper secretion of hormones.

3. ADRENAL HORMONES • Each adrenal is composed of two endocrine organs, one surrounding the other. • The outer layers composing the adrenal cortex secrete a variety of steroid hormones. • The inner portion, the adrenal medulla, secretes catecholamines.

5. Steroidogenic pathways for the major steroid hormones

6. The adrenal cortex • The adrenal cortex consists of three layers or zones: • The zonaglomerulosa, the outermost layer. • The zonafasciculata, the middle and largest portion. • The zonareticularis, the innermost zone.

7. The adrenal steroids • Mineralocorticoids, mainly aldosterone, influence mineral (electrolyte) balance, specifically Na+ and K+ balance. • Glucocorticoids, primarily cortisol, play a major role in glucose metabolism as well as in protein and lipid metabolism and in adaptation to stress. • Sex hormones are identical or similar to those produced by the gonads (testes in males, ovaries in females). The most abundant and physiologically important of the adrenocortical sex hormones is dehydroepiandrosterone, an androgen, or “male” sex hormone.

8. The adrenal steroids • Aldosterone is produced exclusively in the zonaglomerulosa. • Cortisol synthesis is limited to the two inner • layers of the cortex, with the zonafasciculata being the major source of this glucocorticoid • Carried in the blood extensively bound to plasma proteins.

9. The adrenal steroids • Cortisol is bound mostly to a plasma protein specific for it called corticosteroid-binding globulin (transcortin), • Aldosterone and dehydroepiandrosterone are largely bound to albumin. • Each of the adrenocortical steroid hormones binds with a receptor specific for it within the cytoplasm of the hormone’s target cells • Mineralocorticoids bind to the mineralocorticoid receptor (MR), • glucocorticoids to the glucocorticoid receptor (GR), and • dehydroepiandrosteroneto the androgen receptor (AR).

10. Aldosterone • The principal site of aldosterone action is on the distal and collecting tubules of the kidney • Promotes Na+retention and enhances K +elimination during the urine formation • induces osmotic retention of H2O • Expanding the ECF volume • Long-term regulation of blood pressure

11. Aldosterone Mineralocorticoids are essential for life: • Without aldosterone, a person rapidly dies from circulatory shock because of the marked fall in plasma volume caused by excessive losses of H2O-holding Na+.

12. Aldosterone • Aldosterone secretion is increased by • activation of the renin-angiotensin-aldosteronesystem (RAAS) by factors related to a reduction in Na+and a fall in blood pressure. • direct stimulation of the adrenal cortex by a rise in plasma K+concentration. • The regulation of aldosterone secretion is largely independent of anterior pituitary control.

14. Glucocorticoids • Cortisol, the primary glucocorticoid, plays an important role in carbohydrate, protein, and fat metabolism; executes significant permissive actions for other hormonal activities; and helps people resist stress. • Metabolic effects The overall effect of cortisol’s metabolic actions is to increase the concentration of blood glucose at the expense of protein and fat stores.

15. Glucocorticoids • Hepatic gluconeogenesis • It inhibits glucose uptake and use by many tissues, but not the brain – increases blood glucose • Protein degradation in many tissues, especially muscle - increases the blood amino acid concentration • Facilitates lipolysis – increase free fatty acids into the blood • Permissiveness: Cortisol must be present in adequate amounts to permit the catecholamines to induce vasoconstriction. • Adaptation to stress

16. Glucocorticoids ANTI-INFLAMMATORY AND IMMUNOSUPPRESSIVE EFFECTS • Cortisolinterferes with almost every step of inflammation. • Blocks production of inflammatory chemical mediators, such as prostaglandins and leukotrienes • Suppresses migration of neutrophils • inhibits proliferation of fibroblasts in wound repair • interfere with antibody production by lymphocytes. • Cortisol in turn has a profound dampening (turning-down) impact on the immune system.

17. The negative-feedback system for cortisol maintains the level of cortisol secretion relatively constant around the set point.

18. Glucocorticoids • Plasma cortisol concentration displays a characteristic diurnal rhythm, with the highest level occurring in the morning and the lowest level at night • Dramatic increases in cortisol secretion, mediated by the central nervous system through enhanced activity of the CRH - ACTH - cortisol system, occur in response to all kinds of stressful situations.

19. Androgen & Estrogen • Under normal circumstances, the adrenal androgens and estrogens are not sufficiently abundant or powerful to induce masculinizing or feminizing effects, respectively. • Dehydroepiandrosterone(DHEA) – a weak androgen • This adrenal androgen governs androgen-dependent processes in the female such as • growth of pubic and axillary (armpit) hair, • enhancement of the pubertal growth spurt, and • development and maintenance of the female sex drive. • ACTH controls the secretion of adrenal androgen but the feed back is outside hypothalamus – pituitary - adrenal axis.

20. ADRENAL MEDULLA

21. ADRENAL MEDULLA • Adrenal Medulla is a specialized ganglion of sympathetic autonomic nervous system. • Adrenal Medulla consists of modified postganglionic sympathetic neurons called CHROMAFFIN CELLS, because of their staining preference for chromium ions.

22. ADRENAL MEDULLA • Preganglionic fibers synapse directly on Chromaffin cells in the adrenal medulla. • The Chromaffin cells secrete hormone into the circulation directly - Epinephrine – 80% - Norepinephrine – 20%

23. Central nervous system Peripheral nervous system Effector organs Acetylcholine Somatic nervous system Skeletal muscle Acetylcholine Norepinephrine Smooth muscle (e.g., in gut) Ganglion Sympathetic division Acetylcholine Epinephrine and norepinephrine Autonomic nervous system Blood vessel Glands Adrenal medulla Acetylcholine Cardiac muscle Para- sympathetic division Ganglion = Preganglionic axons (sympathetic) = Postganglionic axons (sympathetic) = Myelination = Preganglionic axons (parasympathetic) = Postganglionic axons (parasympathetic)

25. ADRENAL MEDULLA • Both epinephrine and Norepinephrine belong to chemical class of CATECHOLAMINES, which are derived from the amino acid TYROSINE. Storage of CATECHOLAMINES in CHROMAFFIN GRANULES • Epinephrine and Norepinephrine are synthesized in the cytosol of adrenal medulla secretary cells and stored in Chromaffin granules. • Epinephrine and Norepinephrine are secreted by exocytosis.

26. ADRENAL MEDULLA Epinephrine and Norepinephrine Effect On Adrenergic Receptors: • Adrenergic Receptors are α1, α2, β1, and β2. • Epinephrine has effect on alpha and beta. more effect on β2, therefore, more effective in bronchial asthma and skeletal muscle [where β2 receptors are present]. Norepinephrine has effect alpha and beta, more effect on β1. NOTE – Epinephrine discharge from adrenal medulla always accompanies generalized sympathetic nervous system discharge.

27. ADRENAL MEDULLA Epinephrine and Norepinephrine Effect On Adrenergic Receptors

29. ADRENAL MEDULLA • Adrenomedullary hormones are not essential for life, but they are very important and work in stress response, regulation of blood pressure and have metabolic effects. • Sympathetic ANS and epinephrine work for fight or flight response that is to combat enemy or flee from danger.

30. ADRENAL MEDULLA METABOLIC EFFECTS OF EPINEPRINE Effect on Carbohydrate 1. Epinephrine mobilizes stored carbohydrates to provide energy for use of muscular work. 2. Epinephrine increases blood glucose level by stimulating both hepatic [liver] Gluconeogenesis and glycogenolysis. 3. Epinephrine also stimulates glycogenolysis in skeletal muscle.

31. ADRENAL MEDULLA 4. Epinephrine increases blood glucose by inhibiting the secretion of insulin and stimulating glucagon. 5. Epinephrine causes lipolysis, therefore, increase blood fatty acids. Therefore, epinephrine metabolic effect are appropriate for fight or flight reaction.

32. ADRENAL MEDULLA OTHER EFFECTS OF EPINEPHRINE • Epinephrine affects CNS alertness – it allows quick thinking, therefore, helps in emergency situations. • CNS stimulant or sedative drugs – work by increasing or decreasing catecholamine in CNS. • Both Epinephrine and Norepinephrine cause sweating. • Epinephrine dilates pupil.

33. ADRENAL MEDULLA CONTROL OF EPINEPHRINE RELEASED BY ADRENAL MEDULLA • Catecholamine secretion from adrenal medulla is controlled by sympathetic input to adrenal medulla by preganglionic fibers coming from thoracic T5-T9 and T10-T11. • Preganglionic fibers release acetylcholine. • Adrenal medulla release Epinephrine and Norepinephrine into the circulation directly.

35. References • Human physiology, Lauralee Sherwood, seventh edition. • Text book physiology by Guyton &Hall,11th edition. • Text book of physiology by Linda .S .Costanzo third edition