NDLI: Cytochrome P450 3A9 catalyzes the metabolism of progesterone and other steroid hormones

Content Provider	Springer Nature Link
Author	Wang, Huamin Napoli, Kimberly L. Strobel, Henry W.
Copyright Year	2000
Abstract	The catalytic requirements and the role of P450 3A9, a female-specific isoform of CYP3A from rat brain, in the metabolism of several steroid hormones were studied using recombinant P450 3A9 protein. The optimal steroid hormone hydroxylase activities of P450 3A9 required cholate but not cytochrome b$_{5}$. P450 3A9 was active in the hydroxylation reactions of testosterone, androstenedione, progesterone and dehydroepiandrosterone (DHEA). No activity of P450 3A9 toward cortisol was detectable under our reconstitution conditions. Among all the steroid hormones examined, female-specific P450 3A9 seemed to catalyze most efficiently the metabolism of progesterone, one of the major female hormones, to form three mono-hydroxylated products, 6β-, 16α-, and 21-hydroxyprogesterone. Our data also showed that P450 3A9 can catalyze the formation of a dihydroxy product, 4-pregnen-6β, 21-diol-3, 20-dione, from progesterone with a turnover number, 1.3 nmol/min/nmol P450. Based on the V$_{max}$/K$_{m}$ values for P450 3A9 using either 21-hydroxprogesterone or 6β-hydroxyprogesterone as a substrate, 4-pregnen-6β, 21-diol-3, 20-dione may be formed either by 6β-hydroxylation of 21-hydroxprogesterone or 21-hydroxylation of 6β-hydroxyprogesterone. As a major isoform of CYP3A expressed in rat brain, the activities of P450 3A9 toward two major neurosteroids, progesterone and DHEA suggested a possible role for P450 3A9 in the metabolism of neurosteroids.
Starting Page	127
Ending Page	135
Page Count	9
File Format	PDF
ISSN	03008177
Journal	Molecular and Cellular Biochemistry
Volume Number	213
Issue Number	1-2
e-ISSN	15734919
Language	English
Publisher	Kluwer Academic Publishers
Publisher Date	2000-01-01
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cardiology Medical Biochemistry Oncology Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Clinical Biochemistry Molecular Biology

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