ADRENOCORTICAL HORMONE

1. ENDO BLOCK 412 ADRENOCORTICAL HORMONE Dr. Shaikh Mujeeb Ahmed Assistant Professor AlMaarefa College

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

6. 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.

7. 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.

8. 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).

9. 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

10. 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+.

11. Aldosterone secretion is increased by • activation of the reninangiotensinaldosteronesystem (RAAS) by factors related to a reduction in Na and a fall in blood pressure and • 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.

13. Steroidogenic pathways for the major steroid hormones

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. 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. ANTI-INFLAMMATORY AND IMMUNOSUPPRESSIVE EFFECTS • Cortisol interferes 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. Control of cortisol secretion The negative-feedback system for cortisol maintains the level of cortisol secretion relatively constant around the set point.

18. 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.

21. Pathophysiology • primary hyperaldosteronism, or Conn’s syndrome)-Adrenal tumor • Secondary hyperaldosteronism- inappropriately high activity of the renin-angiotensin-aldosterone system • Cortisol hypersecretion - (Cushing’s syndrome) • Adrenal androgen hypersecretion – adrenogenital syndrome,

23. Hormonal interrelationships in adrenogenital syndrome