title: Inhibition of human steroidogenic cytochrome P450 c17 by 21-hydroxypregnenolone and related steroid hormones.
abstract: The effects of 21-hydroxypregnenolone and related steroids such as deoxycorticosterone (DOC; 21-hydroxyprogesterone), cortisol, and corticosterone on progesterone 17α-hydroxylase activity by steroidogenic cytochrome P450 c17 (CYP17) were investigated. 21-Hydroxypregnenolone contains a hydroxyl group at C3 in the A cyclic hydrocarbon ring and a double bond at C5 in the B cyclic hydrocarbon ring, whereas DOC, cortisol, and corticosterone contain a ketone group at C3 and a double bond at C4 in the A cyclic hydrocarbon ring. No marked inhibition was observed for DOC, cortisol, and corticosterone at 100 μM concentration. Nonetheless, 21-hydroxypregnenolone exhibited competitive inhibition of progesterone 17α-hydroxylation activity by CYP17 with a Ki value of 36.4 µM. These results suggest that a hydroxyl group at C3 in the A ring and a double bond at C5 in the B ring in steroid hormones are important for the substrate recognition of CYP17.
authors.affiliation: Division of Natural Science, Osaka Kyoiku University, Osaka, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niwa
authors.forename: Hiroko
authors.initials: H
authors.lastname: Imamura
authors.forename: Masanao
authors.initials: M
authors.lastname: Katagiri
mesh_terms: D006907:17-alpha-Hydroxypregnenolone / Q000737:chemistry / Q000378:metabolism*; D065607:Cytochrome P-450 Enzyme Inhibitors; D006801:Humans; D013254:Steroid 17-alpha-Hydroxylase / Q000737:chemistry / Q000378:metabolism*; D013256:Steroids / Q000737:chemistry / Q000378:metabolism*
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D013256:Steroids; D006907:17-alpha-Hydroxypregnenolone; C052374:21-hydroxypregnenolone; D013254:Steroid 17-alpha-Hydroxylase