Androstenedione is an endogenous weak androgen steroid hormone that is a precursor of testosterone and other androgens, as well as of estrogens like estrone . Its metabolism occurs primarily in the endoplasmic reticulum (membrane-associated enzymes are coloured dark green in the image). Conversion of androstenedione to testosterone requires the enzyme testosterone 17-beta-dehydrogenase 3. Conversion of androstenedione to estrone involves three successive reactions catalyzed by the enzyme aromatase (cytochrome P450 19A1). Androstenedione can also be converted into etiocholanolone glucuronide, androsterone glucuronide, and adrenosterone. The three-reaction subpathway to synthesize etiocholanolone glucuronide begins with the enzyme 3-oxo-5-beta-steroid 4-dehydrogenase catalyzing the conversion of androstenedione to etiocholanedione. This is followed by the conversion of etiocholanedione to etiocholanolone which is catalyzed by aldo-keto reductase family 1 member C4. Lastly, the large membrane-associated multimer UDP-glucuronosyltransferase 1-1 catalyzes the conversion of etiocholanolone to etiocholanolone glucuronide. The three-reaction subpathway to synthesize androsterone glucuronide begins with the conversion of androstenedione to androstanedione via 3-oxo-5-alpha-steroid 4-dehydrogenase 1. Anstrostanedione is then converted into androsterone via aldo-keto reductase family 1 member C4. The last reaction to form androsterone glucuronide is catalyzed by the large multimer UDP-glucuronosyltransferase 1-1. The two-reaction subpathway to synthesize adrenosterone begins in the mitochondrial inner membrane where androstenedione is first converted into 11beta-hydroxyandrost-4-ene-3,17-dione by the enzyme cytochrome P450 11B1. Following transport to the endoplasmic reticulum, 11beta-hydroxyandrost-4-ene-3,17-dione is converted into adrenosterone via corticosteroid 11-beta-dehydrogenase isozyme 1.

Androstenedione Metabolism References