In this article we will discuss about Adrenocortical Hormones in Adrenal Gland. After reading this article you will learn about: 1. Subject matter of Adrenocortical Hormones 2. Source of Adrenocortical Hormones 3. Biosynthesis 4. Control 5. Transport 6. Catabolism.
Subject Matter of Adrenocortical Hormones:
Adrenal gland is one of the important endocrine gland which secretes various hormones. Histologically, adrenal cortex secretes adrenocortical steroid hormones. Kendall et al. (1936) obtained crystalline extracts of the adrenal cortex. In 1945, active steroids were extracted from this zone. Three active steroid hormones of adrenal cortex are mineralocorticoids, glucocorticoids and sex steroids.
Source of Adrenocortical Hormones:
Adrenal cortex is histologically divided into three zones, each zone secrete each hormone.
Mineralocorticoids and glucocorticoids are C21 steroids whereas androstenedione is C19 steroid.
Biosynthesis of Adrenocortical Hormone:
Synthesis of adrenocortical steroid hormones is complicated phenomenon.
The synthesis occurs in following steps:
(A) Conversion of cholesterol to pregnenolone:
The adrenal steroid hormones are synthesized from precursor cholesterol molecule. Cholesterol is mostly derived from plasma, but a small portion is synthesized in situ from acetyl CoA. Much of the cholesterol in the adrenal is esterified and steroid in cytoplasmic lipid droplets.
Upon stimulation of the adrenal by ACTH (or cAMP), an esterase is activated, and the free cholesterol formed is transported into the mitochondrion, where cytochrome P450 side chain cleavage enzyme (P450 sec) converts cholesterol to pregnenolone. Pregnenolone acts as a pivot for synthesis of all adrenocorticosteroids. Pregnenolone is then released from the mitochondria and enter into the smooth ER.
(B) Pregnenolone to different adrenocorticosteroids:
Pregnenolone leads to the synthesis of three hormones by successive reactions.
1. Mineralocorticoid synthesis or aldosterone synthesis:
In the zona glomerulosa, pregnenolone is converted to progesterone by the action two smooth endoplasmic reticulum enzymes 3β-OHSD and ∆5, 4 isomerase. Progesterone is then hydroxylated at C21 position to form 11- deoxycorticosterone by the actions of microsomal enzyme 21-hydroxylase.
11-deoxycorticosterone is transferred into mitochondria where next hydroxylation at C11 position, produces corticosterone by the action of 11 β-hydroxylase. The 18-hydroxylase acts on corticosterone to form 18-hydroxycorticosterone.
18-hydroxycorticosterone has its C18 hydroxyl group oxidized to an aldehyde groups by 18-hydroxysteroid dehydrogenase, to be changed into the aldosterone.
2. Glucocorticoids synthesis:
In the zona fasiculata cells during glucocorticoid synthesis cholesterol is converted to pregnenolone like mineralocorticoid synthesis. Pregnenolone follows Cortisol synthesis in one hand and corticosterone synthesis on other hand.
Cortisol synthesis requires three hydroxylases that act sequentially on C17 C21 and C11 positions. The first two reactions are rapid, while C11 hydroxylation is relatively slow. Pregnenolone is changed successively through 1 7-hydroxypregnenolone and 1 7-hydroxyprogesterone to 11-deoxycortisol by the actions of microsomal enzymes—1 7α-hydroxylase, 3β-OHSD, ∆5,4 isomerase and 21 hydroxylase respectively. 11 -deoxycortisol is then trans-located to mitochondria, where it is hydroxylated by mitochondrial enzyme 11 β-hydroxylase to produce Cortisol which is the most potent glucocorticoid hormone in humans.
A small amount of pregnenolone on other hand gives rise to another glucocorticoid hormone corticosterone. Corticosterone biosynthesis takes place through progesterone like aldosterone pathway.
3. Sex steroid synthesis:
The zona reticularis cells mainly take part in this synthesis. In adrenal sex steroid synthesis, basic pregnenolone formation takes place from cholesterol like other adrenocorticosteroid synthesis. The C17-side chain of small amounts of 1 7-hydroxypregnenolone, is oxidatively cleaved away and give rise to dehydroepiandrosterone (DHEA) under the action of microsomal 1 7, 20-Lyase.
Most of DHEA is rapidly modified by the addition of sulfate, about half of which occurs in the adrenal and the rest in the liver. DHEA sulfate is inactive, but removal of the sulfate results in reactivation. 3β-OHSD and ∆5,4 isomerase convert DHEA into more potent sex steroid androstenedione (Fig. 6.1 7).
Control of Adrenocortical Hormones:
The synthesis and release of adrenocorticosteroids is controlled by pituitary ACTH. Increase in the concentration of glucocorticoids in blood inhibits the secretion of ACTH by negative feedback mechanism. ACTH-RH of hypothalamus controls the secretion of pituitary ACTH. The different factors like stress, cold, excitement, diurnal rhythm etc. control the secretion of hypothalamus (Fig. 6.18)
Mineralocorticoids are mainly regulated by plasma concentrations of K+ and Na+, renin-angiotensin system.
Transport of Adrenocortical Hormones:
Glucocorticoids are transported through plasma α-globulin, called transcortin or Corticosteroid Binding Globulin (CBG). Mineralocorticoid does not have a specific plasma transport protein, but it forms a very weak association with albumin. Sex steroid is transported through plasma protein.
Catabolism of Adrenocortical Hormones:
Mineralocorticoid is rapidly cleared from the plasma by the liver. The liver forms tetrahydroaldosterone glucuronide which is excreted via urine. Androstenedione and DHEA are excreted as 1 7-keto compounds. Glucocorticoids are metabolised in the liver and excreted in urine as conjugates with glucuronide or sulfates.