17-Hydroxyprogesterone

17-Hydroxyprogesterone (17-OHP) is a naturally occurring steroid hormone involved in the steroidogenesis of glucocorticoids and sex steroids. It is a derivative of progesterone, with a hydroxyl group at the 17th carbon position, hence its name. 17-OHP plays a crucial role in the biosynthesis of cortisol in the adrenal glands. Its production is stimulated by the adrenocorticotropic hormone (ACTH), released by the pituitary gland.

Biosynthesis and Regulation

17-OHP is synthesized from pregnenolone via the enzyme 17α-hydroxylase, encoded by the CYP17A1 gene. This enzyme is part of the steroidogenesis pathway that converts cholesterol into sex steroids and glucocorticoids. The production of 17-OHP is primarily regulated by ACTH, which is controlled by the hypothalamus through the release of corticotropin-releasing hormone (CRH).

Function

The primary function of 17-OHP is as an intermediate in the synthesis of glucocorticoids and androgens. It is converted to 11-Deoxycortisol by the enzyme 21-hydroxylase for cortisol synthesis. In the sex steroid pathway, 17-OHP can be converted into androstenedione, a precursor for both testosterone and estrone.

Clinical Significance

1. 1. 1. Congenital Adrenal Hyperplasia###

Elevated levels of 17-OHP are associated with congenital adrenal hyperplasia (CAH), a genetic disorder affecting steroidogenesis. CAH results from mutations in enzymes involved in steroid synthesis, most commonly 21-hydroxylase. This leads to an accumulation of 17-OHP, which can be converted into androgens, causing virilization and other health issues.

1. 1. 1. Diagnostic Use###

Measurement of 17-OHP levels in the blood is used in the neonatal screening for CAH. Elevated levels may indicate the presence of the disorder, prompting further diagnostic testing and treatment. It is also measured in adults to diagnose or monitor treatment in individuals with suspected or known CAH.

Treatment

Management of conditions associated with abnormal 17-OHP levels, such as CAH, involves glucocorticoid replacement therapy to reduce ACTH levels and thus decrease the production of 17-OHP and androgens. This helps in controlling the symptoms associated with excess androgen production.

Pharmacology

While 17-OHP itself is not used therapeutically, its analogs, such as hydroxyprogesterone caproate, have been used in the prevention of preterm birth in pregnant women with a history of preterm delivery.

See Also

• Steroid hormone
• Adrenal gland
• Congenital adrenal hyperplasia
• Cortisol
• Androstenedione