Androstenedione and testosterone biosynthesis and metabolism p.1

Androstenedione and testosterone biosynthesis and metabolism part 1

Androstenedione is a 19-carbon steroid hormone produced as an intermediate step in the biochemical pathway that produces the androgen Testosterone and the estrogens Estrone and Estradiol.

Androstenedione originates either from the conversion of Dehydroepiandrosterone or from 17-alpha-Hydroxyprogesterone. These two metabolites have the common precursor - 17-alpha-Hydroxypregnenolone and they are produced as results of different transformations. The first one - formation of Dehydroepiandrosterone catalyzed by Cytochrome P450, family 17, subfamily A, polypeptide 1 (CYP17) [1], [2], [3]. And the second reaction is mediated by Hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 (HSD3B1) [4], [5], and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2 (HSD3B2) [6], [7], [8], [9] with 17-alpha-Hydroxyprogesterone as a product. 17-alpha-Hydroxypregnenolone is a product of oxidative metabolism of Cholesterol.

Dehydroepiandrosterone comes into subsequent oxidative transformation with production of 16Alpha-hydroxydehydroepiandrosterone. This oxidation is catalyzed by Cytochrome P450, family 3, subfamily A, polypeptide 7 (CYP3A7) [10], [11], [12] and Cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) [10], [11], [13]. Oxidative metabolite of this reaction as well as Dehydroepiandrosterone can be further sulfated by steroid sulfatase (microsomal), isozyme S (STS) [14], [15], [16]. Dehydroepiandrosterone and Dehydroepiandrosterone sulfate can be transformed into other compounds with hormonal activity, Androstendiol and Androstendiol sulfate, respectively. These two reactions are catalyzed by Hydroxysteroid (17-beta) dehydrogenase 1 (HSD17B1) [17], [18], Hydroxysteroid (17-beta) dehydrogenase 2 (HSD17B2) [19], [20], [21], and Hydroxysteroid (17-beta) dehydrogenase 7 (HSD17B7) [22], [23], [24].

Androstendiol and Androstenedione are further converted to Testosterone. Formation of Testosterone from Androstendiol is catalyzed by HSD3B1 [25], [26] and HSD3B2 [26], [27], [28], whereas Hydroxysteroid (17-beta) dehydrogenase 3 (HSD17B3), HSD17B7, HSD17B2 and HSD17B1 catalyze formation of testosterone from Androstenedione [20], [21], [22], [23], [29], [30], [31], [32], [33], [34].

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