Endocrine Physiology The Adrenal Gland Part 1 Dr

Endocrine Physiology The Adrenal Gland (Part 1) Dr. Mohd. Aslam Professor of Physiology Department of Physiology

Adrenal (Suprarenal) Glands • Adrenal glands are paired, Cortex Medulla pyramid-shaped organs at the top of the kidneys. • Weigh 6 -10 g. • Structurally and functionally, they are two glands in one • Adrenal cortex (80 -90%)– glandular tissue derived from embryonic mesoderm • Adrenal medulla (10 -20%)– formed from neural ectoderm, can be considered a modified sympathetic ganglion

Adrenal Cortex • Synthesizes and releases steroid hormones (corticosteroids) • Different corticosteroids are produced in each of the three layers: • Zona glomerulosa – mineralocorticoids (mainly aldosterone) • Zona fasciculata – glucocorticoids +Androgens (mainly CORTISOL and corticosterone) • Zona reticularis – gonadocorticoids + glucocorticoids. ( TESTOSTERONE) (mainly dehydroepi. Androsterone DHEA)

Adrenal Gland Guyton and Hall

Histology of the Adrenal Cortex • Three layers, each with major hormone product. - Zone Glomerulosa 10% - Zona Fasciculata 80% - Zona reticularis 10%

Adrenal Cortex Salt Sugar Sex

HPA Axis

Steroid Hormones: Structure

Steroid Hormones Synthesis • Steroids are derivatives of cholesterol • Cholesterol is from the lipid droplets in cortical cells • Removed cholesterol is replenished by cholesterol in LDL in blood or synthesized from acetate - LDL is a complex composed of cholesterol, phospholipids, triglycerides, and proteins (proteins and phospholipids make LDL soluble in blood). - LDL is taken into cells via LDL receptors, and broken down into esterified cholesterol, and then free cholesterol:

Steroid Hormones Synthesis (Cont. ) • Steroid hormones are synthesized and secreted on demand (not stored) • The first and rate-limiting step in the synthesis of all steroid hormones is conversion of cholesterol to pregnenolone by the enzyme cholesterol dismolase (cholesterol side chain cleavage enzyme (SCC)) • Newly synthesized steroid hormones are rapidly secreted from the cell • Following secretion, all steroids bind to some extent to plasma proteins: CBG (corticosteroid binding globulin) and albumin

Steroidogenesis: Steroidogenesis entails processes by which cholesterol is converted to biologically active steroid hormones

Genetic Defects in Adrenal Steroidogenesis • Congenital adrenal hyperplasias: Congenital adrenal hyperplasia (CAH) are any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of cortisol from cholesterol by the adrenal glands (steroidogenesis). cortisol ACTH Adrenal hyperplasia

Congenital adrenal hyperplasias • 21 -hydroxylase (P 450 c 21) deficiency: cortisol, corticosterone, and aldosterone deficiency *ACTH Adrenal hypertrophy and high amounts of androgen * Virilization of female (masculanization)

Steroid Hormones: Action Guyton and Hall

Hormones of adrenal cortex production mg/day concentr. ng/ml activity MINERAL. activity GLUCO. aldosterone 0. 05 -0. 15 90% deoxycorticosterone 0. 6 0. 15 1/15 corticosterone 1 -4 2 -4 1/50 4% cortisol 8 -25 40 -180 1/400 95% DHEA 7 -15 5

1 - Cortisol is at 1000 fold higher concentrations than aldosterone 2 - Corticosterone >>>>aldosterone 3 - Cortisol binds well to the mineralocorticoid receptor

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