androstenedione
Summary
Androstenedione is a weak endogenous androgen steroid hormone produced by the adrenal glands, gonads (testes and ovaries), and placenta. It serves as a key precursor in the biosynthesis of both testosterone and estrone, sitting at a critical branch point in steroidogenesis. Elevated levels are a hallmark of congenital adrenal hyperplasia and PCOS.
Detail
Androstenedione (4-androstene-3,17-dione) is synthesized from 17-hydroxyprogesterone via 17,20-lyase activity of CYP17A1 in the adrenal cortex (zona reticularis) and gonads. It is converted peripherally by 17β-hydroxysteroid dehydrogenase to testosterone, and by aromatase (CYP19A1) to estrone, making it a pivotal intermediate linking adrenal/gonadal steroidogenesis to sex hormone production.
Clinical significance: In congenital adrenal hyperplasia (most commonly 21-hydroxylase deficiency), cortisol synthesis is blocked, shunting precursors toward androgen production, causing markedly elevated androstenedione and testosterone, leading to virilization in females (ambiguous genitalia) and precocious puberty in males. In polycystic ovary syndrome (PCOS), ovarian theca cells overproduce androstenedione and testosterone, contributing to hirsutism, acne, and oligomenorrhea. Androstenedione is also measured clinically to assess adrenal and gonadal androgen excess, and was historically used (and banned) as a performance-enhancing supplement due to its conversion to testosterone.
Laboratory correlation: Elevated androstenedione with low cortisol and elevated 17-hydroxyprogesterone supports a diagnosis of 21-hydroxylase deficiency CAH. In adrenal or ovarian tumors secreting androgens, androstenedione may also be elevated alongside DHEA-S and testosterone.
Sources
- First Aid for the USMLE Step 1
- Guyton and Hall Textbook of Medical Physiology
- Harrison's Principles of Internal Medicine
- UpToDate: Congenital adrenal hyperplasia
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