Human Biochemistry, Volume 2 - Murray R. 1993

Biochemistry of Intracellular and Intercellular Communications
Adrenal Cortex Hormones
Secretion, Transport, and Metabolism of Adrenal Steroid Hormones

Secretion

Steroid Hormones are practically not stored (and perhaps not stored at all) in adrenal Cells, but are instead released into the plasma as they are synthesized. Cortisol secretion occurs in a pulsatile manner determined by the circadian rhythm of ACTH release.

Transport in Blood

A. Glucocorticoids. In Blood Plasma, cortisol exists in both protein-bound and free forms. The primary plasma binding protein is an alpha-globulin known as transcortin (corticosteroid-binding globulin). Transcortin is produced in the Liver, and its synthesis, like that of thyroxine-binding globulin (TBG), is stimulated by estrogens. When plasma cortisol levels are within the normal range, the majority of the hormone is bound to transcortin, with a significantly smaller amount bound to albumin. The strength of this binding determines the biological half-life of various glucocorticoids. For instance, cortisol binds tightly to transcortin and has a t_1/2 of 1.5–2 hours, whereas corticosterone, which binds less tightly, has a t_1/2 of less than 1 hour. Transcortin binds more than just glucocorticoids; deoxycorticosterone and progesterone interact with this protein with sufficiently high affinity to compete with cortisol. Unbound (free) cortisol accounts for about 8% of the total hormone in blood plasma and represents the biologically active fraction.

B. Mineralocorticoids. Aldosterone, the most potent of the natural mineralocorticoids, lacks a specific transport protein in the plasma, but forms weak bonds with albumin. Corticosterone and 11-deoxycorticosterone, Steroids with mineralocorticoid activity, bind to transcortin. This information is crucial for understanding the MECHANISM OF ACTION of aldosterone (see below).

METABOLISM and Excretion

A. Glucocorticoids. Cortisol and its metabolic products account for about 80% of plasma 17-hydroxycorticoids, with the remaining 20% consisting of cortisone and 11-deoxycortisol. Approximately half of the total cortisol (as well as cortisone and 11-deoxycortisol) circulates in the form of reduced dihydro- and tetrahydroderivatives. These are formed by the reduction of double bonds in ring A via an NADPH-dependent dehydrogenase reaction, as well as the reduction of the 3-keto group in a reversible dehydrogenase reaction. Significant amounts of all these compounds undergo further modification by forming conjugates at the C-3 position with glucuronide and, to a lesser extent, with sulfate. This modification, which occurs primarily in the liver, renders the lipophilic steroid molecules Water-soluble and capable of excretion. In humans, the majority of conjugated steroids entering the intestine via Bile are reabsorbed, entering enterohepatic Circulation. About 70% of conjugated steroids are excreted in the urine, 20% in the feces, and the remainder is eliminated through the Skin.

B. Mineralocorticoids. Aldosterone is rapidly cleared from the blood by the liver, which is undoubtedly related to the absence of a specific carrier protein in the plasma. In the liver, the hormone is converted into tetrahydroaldosterone-3-glucuronide, which is excreted in the urine.

C. Androgens. Androgens are eliminated from the body as 17-ketosteroids, including DHEA (sulfate), as well as androstenedione and its metabolites. Testosterone, secreted by the Adrenal Glands in small amounts, is not classified as a 17-Ketosteroid; however, in the liver, about half of all testosterone is converted into androsterone and etiocholanolone, which are 17-ketosteroids.