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 stepin the biochemical pathway that produces the androgen Testosterone and theestrogens Estrone and Estradiol.
Androstenedione originates either from the conversion ofDehydroepiandrosterone or from 17-alpha-Hydroxyprogesterone. These twometabolites have the common precursor - 17-alpha-Hydroxypregnenolone and they areproduced as results of different transformations. The first one - formation ofDehydroepiandrosterone catalyzed by Cytochrome P450, family 17, subfamily A,polypeptide 1 ( CYP17 ) [1], [2], [3]. Andthe second reaction is mediated by Hydroxy-delta-5-steroid dehydrogenase, 3 beta- andsteroid delta-isomerase 1 ( HSD3B1 ) [4], [5], andhydroxy-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 ofCholesterol.
Dehydroepiandrosterone comes into subsequent oxidative transformation withproduction of 16Alpha-hydroxydehydroepiandrosterone. This oxidation is catalyzedby Cytochrome P450, family 3, subfamily A, polypeptide 7 ( CYP3A7) [10], [11], [12] and Cytochrome P450, family 3, subfamily A,polypeptide 4 ( CYP3A4) [13], [10], [11].Oxidative metabolite of this reaction as well as Dehydroepiandrosterone can befurther sulfated by steroid sulfatase (microsomal), isozyme S ( STS ) [14], [15], [16], [15], [14].Dehydroepiandrosterone and Dehydroepiandrosterone sulfate can betransformed into other compounds with hormonal activity, Androstendiol andAndrostendiol sulfate, respectively. These two reactions are catalyzed byHydroxysteroid (17-beta) dehydrogenase 1 ( HSD17B1) [17], [18], [17], [18], Hydroxysteroid (17-beta) dehydrogenase 2 (HSD17B2) [19], [20], [20], [21],and Hydroxysteroid (17-beta) dehydrogenase 7 ( HSD17B7 ) [22], [23], [23], [24].
Androstendiol and Androstenedione are further converted toTestosterone. Formation of Testosterone from Androstendiol iscatalyzed by HSD3B1 [25], [26] and HSD3B2 [27], [28], [26], whereas Hydroxysteroid (17-beta)dehydrogenase 3 ( HSD17B3 ), HSD17B7, HSD17B2 and HSD17B1catalyze formation of testosterone from Androstenedione [29], [30], [31], [32], [22], [33], [23], [34], [30], [21], [20].
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