Estrogen biosynthesis

Estrogen biosynthesis.

The biosynthesis of estrogen is initiated by the synthesis of Androstenedione, 19-carbon steroid hormone, from cholesterol. Then this compound is converted to estrogens Estrone or Estradiol, either immediately or through Testosterone, which may also be derived from cholesterol.

Reduction of Androstenedione to Testosterone requires Hydroxysteroid (17-beta) dehydrogenase 2 (HSD17B2) [1], [2] and Hydroxysteroid (17-beta) dehydrogenase 3 (HSD17B3) [3], [4], [5]. The reverse reaction, oxidation of Testosterone at 17-position to form Androstenedione, is catalyzed by monooxygenase Cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) [6].

Androstenedione undergoes a three-step A-ring aromatization to Estrone catalyzed by monooxyganases: aromatase Cytochrome P450, family 19, subfamily A, polypeptide 1 (CYP19) [7] and Cytochrome P450, family 11, subfamily B, polypeptide 1 (CYP11B1) [8]. The first intermediate reaction is the formation of 19-Hydroxyandrostenedione [9], which then is converted to Androst-4-en-3,17,19-trione [7], [9] followed by oxidation to Estrone [7], [9].

Another pathway of Estrone biosynthesis is oxidation of 17-alpha-Estradiol by Estradiol 17a-dehydrogenase (1.1.1.148) [10].

Aromatase CYP19 also catalyzes oxidation of Testosterone to Estradiol [7], [11]. The first step is formation of 19-Hydroxytestosterone [12], which in turn is oxidized to 19-Oxotestosterone [11], and then to Estradiol [11], [13], similar to Androstenedione catabolism to Estrone.

Another steroid substrate, which undergoes a CYP19-catalyzed three-step aromatization, is 16alpha-Hydroxyandrostenedione [14], [15]. The final product of that oxidation is 16alpha-Hydroxyestrone.

Interconversion of Estradiol and Estrone requires Hydroxysteroid (17-beta) dehydrogenases 1 (HSD17B1) [16], 7 (HSD17B7) [17] and 8 (HSD17B8) [18].

References:

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