Norharman (beta-carboline) as a potent inhibitory ligand for steroidogenic cytochromes P450 (CYP11 and CYP17).
Norharman (beta-carboline, a so-called mammalian alkaloid) is identified as a high-affinity type II ligand for two steroidogenic cytochromes P450, viz. CYP11 in rat adrenal mitochondria and CYP17 in rat testicular microsomes. Progesterone binding to CYP17 is competitively inhibited, with Ki = 2.6 microM norharman, whereas harman, tetrahydronorharman and tetrahydroharman are nearly ineffective. The potential role of norharman as an endogenous modulator of steroid hormone biosynthesis and as a basic drug for development of more specific cytochrome P450 inhibitors is emphasized.
Kühn-Velten
W N
WN
Department of Obstetrics and Gynecology, Heinrich-Heine-University, Düsseldorf, Germany.
D000311:Adrenal Glands / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002243:Carbolines; D006247:Harmine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D013252:Steroid 11-beta-Hydroxylase / Q000378:metabolism*; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism*; D013737:Testis / Q000187:drug effects / Q000201:enzymology*
D002243:Carbolines; D006247:Harmine; D011374:Progesterone; C005010:harman; C010262:norharman; D013254:Steroid 17-alpha-Hydroxylase; D013252:Steroid 11-beta-Hydroxylase