2. At the end of this lecture, the student should be able to: Enumerate the adrenocortical and adrenomedullary hormones Describe the chemical nature, source and actions of mineralocorticoids Describe the chemical nature, source and actions of Glucocorticoids Describe the chemical nature, source and actions of adrenal androgens Describe the feed back control of adrenocortical hormones.

3.  Each adrenal gland is composed of two endocrine organs: (A) Adrenal medulla (The inner portion) : It secretes Adrenaline, Noradrenaline & Dopamine in to blood. (B) Adrenal cortex (The three outer layers): Zona Glomerulosa: the outermost layer that secretes Mineralocorticoids (Aldosterone). Zona Fasciculata: secretes Glucocorticoids (Cortisol). Zona Reticularis: the innermost layer that secretes Sex hormones (dehydroepiandrosterone = DHEA).

5. 1.Mineralocorticoids, mainly aldosterone, influence minerals (electrolytes) balance, specifically Na + & K + balance. 2.Glucocorticoids, primarily cortisol, play a major role in glucose metabolism as well as in protein and lipid metabolism and in adaptation to stress. 3.Sex hormones, are similar to those produced by gonads. The most abundant and physiologically important of the adrenal androgen is dehydroepiandrosterone (DHEA).

6. Mechanism of action of Steroids

8. 1 - MINERALOCORTICOIDS ALDOSTERONE Functions: 1)↑ Reabsorption of Na + from distal renal tubules. 2)↑ Excretion of K + from distal renal tubules. 3)↑ Excretion of H + ions from distal renal tubules. 4)↑ Water reabsorption along with Na +. 5)  Na + content of sweat, saliva and other secretions. 6)Acts as a long-term regulator of blood pressure

9. CONTROL OF ALDOSTERONE SECRETION  Without aldosterone, a person rapidly dies from circulatory shock because of the marked fall in plasma volume caused by excessive losses of H 2 O- holding Na +.  Aldosterone secretion is controlled by: 1- ↓ Plasma Na + or ↑ K + :  Plasma Na + by 10 % or  plasma K + by 10 %  stimulate synthesis and release of aldosterone by a direct action. 2- Secretion of renin & Angiotensin II formation: Angiotensin II & III stimulate zona glomerulosa to produce Aldosterone.

12. CONTROL OF ALDOSTERONE SECRETION 3- ACTH: ACTH is not a major factor in control of aldosterone. ACTH in large dose (greater than the dose that stimulates maximum cortisol secretion)  transient  in aldosterone. 4- Atrial Natriuretic Factor (ANF): Inhibits aldosterone and renin secretion in a negative feedback manner. ANP decreases responsiveness of zona glomerulosa to stimuli that normally increase aldosterone secretion.

13. HYPERALDOSTERONISM Primary hyperaldosteronism (Conn’s syndrome): – Cause: Adrenal tumor of aldosterone –secreting cells Secondary hyperaldosteronism: – Cause: inappropriately high activity of the renin-angiotensin- aldosterone system

14. 1- PRIMARY ALDOSTERONISM (CONN’S SYNDROME) Aldosterone-secreting tumors of adrenal cortex   aldosterone. Na + retention  hypertension. K + excretion  hypokalemia Alkalosis  tetany. Polyuria due to renal damage and loss of concentrating ability (= Hypokalaemic nephropathy). No edema (due to Aldosterone escape phenomenon).

15. 2- SECONDARY ALDOSTERONISM Renal ischemia   renin   Angiotensin II   aldosterone. Or Hyperplasia of JGA in kidney  renin All signs of aldosterone excess appear & edema occurs.

16. 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. It is secreted from zona fasciculata. Cortisol has anti-stress & anti-shock effects. Excess cortisol has anti-inflammatory & anti- allergic effects.

17. Functions of cortisol 1)Protein metabolism: It inhibits amino acid uptake and protein synthesis in extrahepatic tissues. Catabolic in muscle, skin and bone. Excess cortisol  severe muscle wasting. 2) CHO metabolism: ↑ Blood glucose level by: ↓ Tissue uptake of glucose. ↓ Conversion of glucose to glucose-6-phosphate (anti-insulin action). ↑ gluconeogenesis in liver. Excess cortisol  diabetogenic.

18. Functions of cortisol 3) Fat metabolism: Mobilization of fat from fat depots to supply energy (Lipolytic ketogenic). Excess cortisol  ketosis. 4) Cardiovascular function: Increase myocardial contractility and vasoconstriction due to enhancement of catecholamine effects (permissive effects of cortisol).

19. Functions of cortisol 5) Anti-stress: Activate energy metabolism. In severe physical or mental stress, cortisol plasma conc. remains at a very high level (up to 10 times the normal value) throughout the day. 6) Anti-allergic: Cortisol inhibits allergic responses. ↓ Histamine synthesis in mast cells and basophils ↓ Kinin synthesis.

20. Functions of cortisol 7) Anti-inflammatory: Cortisol inhibits all stages of inflammatory process. It has a stabilizing action on lysosomal membranes of leucocytes. ↓inflammatory chemical mediators as prostaglandins & Interleukins. It suppresses migration of neutrophils. It inhibits proliferation of fibroblasts in wound repair

21. Functions of cortisol 8) Cortisol impedes development of cartilage: ↓ Absorption of Ca ++ from GIT by antagonizing effect of vitamin D. ↑ Ca ++ loss in urine. Excess cortisol  osteoporosis of bones especially vertebrae. 9) Immunosuppressive: Cortisol inhibits normal immune response. ↓ Circulating lymphocytes, basophils and eosinophils. ↓ Antibody production. Disadvantage: it causes spread of infection (as TB). Advantage: It is used in treatment of autoimmune disorders.

22. Functions of cortisol 10) On GIT: Cortisol increases gastric acidity. Excess cortisol  peptic ulcer. 11) On water & electrolytes: Excess cortisol  Na + & water retention and  K + excretion (aldosterone like action). 12) On CNS: Increase EEG activity. Excess cortisol  psychosis.

23.  –ve feedback system for cortisol maintains the level of cortisol secretion relatively constant around the set point.  Cortisol produces -ve feedback to inhibit hypothalamic CRH and anterior pituitary ACTH.

24.  Plasma cortisol concentration displays a characteristic circadian rhythm, with the highest level occurring in the morning and the lowest level at night.

25. Adrenal cortex secretes small amounts of androgens, estrogens & progesterone. Under normal circumstances, adrenal androgens and estrogens are not sufficiently abundant or powerful to induce masculinizing or feminizing effects, respectively. Dehydroepiandrosterone (DHEA) is a weak androgen that governs androgen-dependent processes in the female such as: 1- Growth of pubic and axillary hair 2- Enhancement of the pubertal growth spurt 3- Development and maintenance of the female sex drive.