4-Androstenedione

4-Androstenedione (also known as 4-AD) is a steroid hormone produced in the adrenal glands, the gonads, and the brain. It is a direct precursor of the hormone testosterone and a metabolite of dehydroepiandrosterone (DHEA).

Production and Metabolism

4-Androstenedione is produced in one of two ways. The primary pathway involves conversion of 17-hydroxypregnenolone to dehydroepiandrosterone by way of 17,20-lyase, with subsequent conversion of DHEA to 4-Androstenedione via the enzyme 3β-hydroxysteroid dehydrogenase. The secondary pathway involves conversion of 17-hydroxyprogesterone, most often a conversion of progesterone, to 4-Androstenedione directly by 17,20-lyase. Thus, 17,20-lyase is required for the synthesis of 4-Androstenedione, whether immediately or one step removed.

The production of adrenal 4-Androstenedione is governed by adrenocorticotrophic hormone (ACTH), whereas production of gonadal 4-Androstenedione is under control by the gonadotropins. In premenopausal women, the adrenal glands and ovaries each produce about half of the total 4-Androstendione (about 3 mg/day). After menopause, 4-Androstenedione production is about halved, primarily due to the reduction of the steroid secreted by the ovary. Nevertheless, 4-Androstenedione is the principal steroid produced by the postmenopausal ovary.

Role in the Body

4-Androstenedione is converted to either testosterone or estrone. Conversion of 4-Androstenedione to testosterone requires the enzyme 17β-hydroxysteroid dehydrogenase, while conversion of 4-Androstenedione to estrone requires the enzyme aromatase.

Medical Use

4-Androstenedione has been used in treatments for symptoms of menopause in women. However, it is not approved by the Food and Drug Administration (FDA) for such use.

Side Effects

Long-term use of 4-Androstenedione can lead to serious health issues including an increased risk of heart disease, cancer, and stroke. It can also cause mood swings, aggression, and other psychological side effects.

See Also

• Steroid hormone
• Testosterone
• Estrone
• Menopause

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