Adrenal Glands Composed of two endocrine systems, medullary and cortical systems. Mesodermal cells contribute to the dev of adrenal cortex, gonads and liver-3 tissues that are active in steroid metabolism in fetus. Adrenals and gonads have in common certain enzymes involved in steroid synthesis, and an inborn defect in one tissue may also involve the other.
Embryology Primordium of fetal adrenal recognized at 3-4 wks gestation cephalad to developing mesonephros . At 5-6 wks gonadal ridge devs steroidogenic cells of gonads and adrenal cortex. Adrenal cells migrate retroperitoneally and gonadal cells caudad .
At 6-8 wks gland enlarges- cells of inner cortex form fetal zone and outer subcapsular rim remains definitive zone. Primordium is then invaded by sympathetic neural cells that form chromaffin cells. In a fetus of 2 mo, adrenals are larger than the kidneys and situated on upper pole of kidney. By 9-12 wks fetal zone has active steroidogenesis .
From 4th mo, kidneys grow rapidly, becoming about twice as large as the adrenals by the end of 6th mo. At term, adrenal is one third the size of the kidney, and the combined wt of both glands is 7–9 g. At birth inner fetal cortex makes up 80% and outer true cortex 20% of the gland. Fetal cortex begins to involute (50% by 1 mo.) Medulla is small and enlarges proportionately over 1 st 6 mos.
At 1 yr each adrenal weighs < 1g Adrenal growth later achieves a wt of 4g each. Zona fasciculata and glomerulosa fully differentiated at 3yrs age. Reticularis fully differentiated at puberty. Early fetal adrenal growth independent of ACTH. From midterm to term, growth and maturation relies on ACTH. Normal pituitary –adrenal feedback operative in 1 st semester.
GROSS STRUCTURE Each adrenal gland in adult is pyramidal in structure (2 - 3 cm wide, 4 - 6 cm long, and 1 cm thick) Lies above and medial to the kidney. Has a fibrous capsule and is surrounded by fat. Medulla accounts for approx 10% of total adrenal weight . Ectopic adrenal tissue (cortical cells), can be located in the retroperitoneal celiac plexus,hilum of spleen,ovaries , scrotum, liver, gallbladder, or cranium
Histology Zona glomerulosa - 15 percent of the adult cortex. Poorly demarcated layer of U-shaped or spherical nests, under the capsule. Penetrated by extensions of the zona fasciculata that may extend to the capsule. Zona fasciculata - 75 percent of cortex Radial cords of cells lying between delicate fibrovascular trabeculae . Large cells with high cytoplasmic -to-nuclear ratio and their "clear" cytoplasm is foamy and vacuolated due to the many lipid inclusions. Innermost zona reticularis is sharply demarcated from both the zona fasciculata and the medulla Anastomosing cords of cells separated by thin-walled sinusoids. Cytoplasm is lipid-poor
First step in adrenal steroid synthesis is the combination of acetyl CoA and squalene to form cholesterol, which is then converted into pregnenolone . Enclosed area contains the core steroidogenic pathway utilized by the adrenal glands and gonads.
17- 17-hydroxylase (CYP17, P450c17) 17,20 - 17,20 lyase (also mediated by CYP17) 3- 3-hydroxysteroid dehydrogenase 21- 21-hydroxylase (CYP21A2, P450c21) 11- 11-hydroxylase (CYP11B1, P450c11) 18- 2-step process of aldosterone synthase (CYP11B2, P450c11as), resulting in the addition of OH group that is then oxidized to an aldehyde group at the 18-C; 17R-17-reductase 5R - 5-reductase DHEA- dehydroepiandrostenedione DHEAS- DHEA sulfate A- aromatase (CYP19).
Regulation of Adrenal Cortex Cortisol Secretion . Glucocorticoid secretion is regulated mainly by ACTH, produced in the anterior pituitary. ACTH is released in secretory bursts of varying amplitude throughout the day and night. normal diurnal rhythm of cortisol secretion is caused by the varying amplitudes of ACTH pulses. Pulses of ACTH and cortisol occur every 30–120min, are highest at time of waking, low in afternoon and evening, and lowest 1-2hr after sleep begins.
CRH synthesized by neurons of the hypothalamic paraventricular nucleus, is the main stimulator of ACTH secretion. Arginine vasopressin augments CRH action. AVP and CRH are secreted in the hypophyseal -portal circulation in a pulses. Cortisol exerts a negative feedback effect on the synthesis and secretion of ACTH, CRH, and AVP. ACTH inhibits its own secretion,at the level of hypothalamus.
Regulation of Aldosterone Secretion. Rate of aldosterone synthesis, 100- to 1000-fold less than that of cortisol . Regulated mainly by the renin-angiotensin system and by K+, (ACTH has only a short-term effect). Triggers- decreased intravascular volume and hyperkalaemia Angiotensin II and III are potent stimulators of aldosterone secretion; angiotensin II is a more potent vasopressor agent.
Renin-angiotensin-aldosterone system and the maintenance of sodium and volume balance.
Regulation of Adrenal Androgen Secretion. Not completely understood. Adrenarche is a maturational process in the adrenal gland that results in increased adrenal androgen secretion at 5-20 years. The process begins before the earliest signs of puberty and continues throughout the years when puberty is occurring. Histologically , it is associated with appearance of the zona reticularis . ACTH stimulates adrenal androgen production acutely . Other stimuli are decrease in expression of 3ß- hydroxysteroid dehydrogenase in the zona reticularis and increases in 17,20-lyase activity owing to phosphorylation or increased cytochrome b5 expression.
Adrenal Steroid Hormone Actions Unliganded glucocorticoid and mineralocorticoid receptors are found in cytosol . Different steroids share bioactivities because they bind to the same receptor A steroid may exert diverse biologic effects in different tissues.
Glucocorticoids . Essential for survival. ‘ glucocorticoid ’ refers to the glucose-regulating properties of these hormones. Multiple effects on carbohydrate, lipid, and protein metabolism, immune, circulatory, and renal function. Influence growth, development, bone metabolism, and central nervous system activity. During stress glucocorticoid secretion can increase up to 10-fold -increased cardiac contractility, co, sensitivity to the pressor effects of the catecholamines and other pressor hormones, work capacity of the skeletal muscles, and capacity to mobilize energy stores.