ADRENAL CORTEX HORMONES AND THEIR DERIVATIVES

ADRENAL CORTEX HORMONES AND THEIR DERIVATIVES :

ADRENAL CORTEX HORMONES AND THEIR DERIVATIVES SHRISHAIL.Y.SHAHAPUR M.PHARM-I PHARMACEUTICAL CHEMISTRY

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INTRODUCTION: The adrenal glands are located near eachkidney and consists of two distinct parts , a ) Adrenal medulla adrenal medula contains Chromaffin cells ( pheochromocytes ). Chromaffin cells secrete the catecholamines epinephrine and norepinephrine Release of catecholamines has been characterized as a “fight or flight” response Catecholamines promote hyperglycemia b ) Adrenal Cortex Cortex synthesize a number of steroid hormones. 80% of an adrenal gland’s total weight. The production of these adrenocortcal hormones or Corticoids has been controlled by the hormone ACTH ( Adrenocorticotropic hormone ) which is produced in the anterior lobe of the pituitary.

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LOCATION OF ADRENAL GLAND

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Structures of important adrenocorticoids :-

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The main physiological functions adrenocorticoids : Control of carbohydrate and protein metabolism. Control the balance of water and electrolytes .

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Biosynthesis of corticoids :

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Fused ABCD ring or steroid ring structure is necessary for pharmacological activity of corticosteroids. Presence of α ,β- group unsaturated ketonic (a double bond between C 4 and C 5 and a ketonic group at C 3 ) is very essential. 2) Substituent’s which significantly increases activity of glucocorticoids and anti-inflammatory activity are α- Flouro at 6 th carbon α- Methyl at C 12 or C 6 and C 16. SAR

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3) Substituent’s which significantly increases activity of mineralocorticoid activity are α- hydroxy at C 16 16 α and 16 β-methyl Ketols on 16 α and 17 α. 4) Substituent’s which increases both mineralocorticoid and glucocorticoid activity. Flouro - 9 α Chloro - 9 α Hydroxy -21 α Methyl -2 α 5) Substituent’s which decreases glucocorticoid activity are Methyl – at C 4 , C 7, C 9 , C 11 and C 21. 6) No retention activity can increased by substituent’s of halogens ( F,Cl,Br ) at 9 th position and activity order is F> Cl >Br.

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Glucocorticoids : Glucocorticoid are the steroid hormone which controles the carbohydrate and protein metabolism 95% of glucocorticoid activity are shown by cortisol Effect of cortisol on protein metabolism Reduction of protein storage in all cells except those of liver – ↑ protein catabolism & ↓ protein synthesis Cortisol increases liver & plasma proteins Mobilizes aminoacids from non hepatic cells, thus increase blood amino acid level. Effects of cortisol on fat metabolism ↑ fat mobilization from adipose Promotes cellular oxidation of fatty acids, thus causing the utilization of fats for energy instead of glucose

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Excess cortisol cause obesity Buffalo like torso Moon face Caused due to excess stimulation of food intake & fat being generated more rapidly than mobilized & oxidized

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Other examples of glucocorticoids :

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Mineralocorticoids : Aldosterone exerts the 90% of the mineralocorticoid activity. Cortisol also have mineralocorticoid activity, but only 1/400 th that of aldosterone Aldosterone increases renal tubular (principal cells) reabsorption of sodium & secretion of potassium Excess aldosterone ↑ ECF volume & arterial pressure, but has only a small effect on plasma sodium concentration Excess aldosterone causes hypokalemia & muscle weakness, & too little aldosterone causes hyperkalemia & cardiac toxicity Excess aldosterone increases tubular (intercalated cells) hydrogen ion secretion, with resultant mild alkalosis Aldosterone stimulates sodium & potassium transport in sweat glands, salivary glands, & intestinal epithelial cells

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Synthesis of Aldosterone

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Other examples of mineralocorticoids : Adrenal Disorders Pheochromocytoma tumor of adrenal medulla, with hypersecretion of (nor-)epinephrine causes  BP,  metabolic rate, hyperglycemia, glycosuria , nervousness, indigestion, sweating

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Cushing syndrome (adrenal tumor, excess ACTH) causes hyperglycemia, hypertension, weakness, edema muscle, bone loss with fat deposition shoulders + face Adrenogenital Syndrome (AGS): Androgen hypersecretion causes enlargement of penis or clitoris and premature onset of puberty. Prenatal AGS in girls can result in masculinized genitals (photo) AGS in women can result in deep voice, beard, body hair

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REFERENCES: 1)Wilson and Glisvold’s ., organic pharm and Medicinal chemistry 11 th Edition. 2) Medicinal chemistry 5 th Edition by Ashutosh Kar . 3) Organic chemistry of natural products, vol -II by Gurdeep R Chatwal . 4) Org.chem ., Chemistry of organic natural products., by O.P Agarwal . 5) Burgers medicinal chemistry, Drug discovery & design , Vol -IV , V-Edition 6) Med.Chem , vol -II, Kadam & Bhothara