Steroid Hormone Synthesis

Steroid hormones are extracellular messengers elaborated by the gonads and the adrenal cortex, plus the placenta in pregnant females. A general feature of steroid hormones is that they are not stored for release after synthesis. Levels of circulating hormones are controlled primarily by their rates of synthesis. This, in turn, is often controlled by signals from the brain.

Steroid hormones are classified into five major categories - progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens.

Pregnenolone is derived from cholesterol and is the precursor of all other steroid hormones. For example, pregnenolone is coverted to progesterone by oxidation of the hydroxyl group to a ketone and isomerization of a double bond (see here). Synthesis of other steroid hormones from progesterone is shown in Figure 19.24.

Note that 17-Hydroxyprogesterone is a branch point between synthesis of the glucocorticoids and the androgens. Thus, deficiency of 17-hydroxylase, the enzyme responsible for catalyzing the synthesis of 17-hydroxyprogesterone, leads to reduced amounts of corstisol (glucocorticoid), androgens, and estrogens.

Note also that the estrogens (e.g., estradiol) are derived from the androgens by aromatization of a ring. This reaction is catalyzed by an enzyme complex called aromatase. Reactions catalyzed by aromatase represent the only known route for synthesis of aromatic rings in animal cells.

Deficiency of 21-hydroxylase inhibits the synthesis of glucocorticoids (e.g., cortisol) and mineralocorticoids (e.g., aldosterone), leading to overproduction of testosterone in the adrenal glands and underproduction of cortisol. The latter effectively increases adrenocorticotropic hormone (ACTH), which stimulates the adrenals to grow and synthesize steroids, exacerbating the testosterone overproduction. This leads to masculinization of females.

Deficiency of 5-reductase, the enzyme that converts testosterone to dihydrotestosterone, decreases effective androgen levels and leads to feminization of males.

Synthetic steroid hormones include the following:

> Diethylstilbestrol, a synthetic estrogen previously used to promote growth of beef cattle, until it was found to be potentially carcinogenic at the levels found in meat from treated cattle.

> Oral contraceptives, such as norethynodrel and mestranol.

Mammalian cells lack the ability to completely degrade steroid compounds. As a result, most become conjugated through their hydroxyl groups to glucuronate or sulfate and are eliminated in the urine. This is why the urine of athletes is used to test for illegal steroid hormone use.

See also: Steroid Metabolism, Steroid Hormones, Cholesterol Biosynthesis, Cholesterol

INTERNET LINKS:

> 1. Steroid Hormone Metabolism

> 2. Androgen and Estrogen Metabolism

> 3. Aromatase Reaction Mechanism