M. Katagiri et al., THE ROLE OF CYTOCHROME B(5) IN THE BIOSYNTHESIS OF ANDROGENS BY HUMANP450C17, Archives of biochemistry and biophysics, 317(2), 1995, pp. 343-347
Human cytochrome b(5) has a profound effect on the 17,20-lyase activit
ies catalyzed by purified, human cytochrome P450c17. It enhances the c
onversion of 17 alpha-hydroxypregnenolone to dehydroepiandrosterone by
13-fold and the conversion of 17 alpha-hydroxyprogesterone to androst
enedione by at least 10-fold. This latter activity is virtually undete
ctable in the absence of cytochrome b(5). Other activities catalyzed b
y P450c17 include 17 alpha-hydroxylation of progesterone and pregnenol
one and are much less influenced by cytochrome b(5). The conversion of
pregnenolone to 17 alpha-hydroxypregnenolone is increased by 2-fold,
while that of progesterone to 17 alpha-hydroxyprogesterone is unchange
d. These studies using purified systems suggest that cytochrome b(5) p
lays a role in regulating the activities of P450c17 to optimize the ba
lance between sex hormone synthesis and glucocorticoid synthesis. In p
articular, they indicate that in human testes which contains a high b(
5)/P450 ratio, 17 alpha-hydraxyprogesterone can serve as an intermedia
te in testosterone production, rather than being a dead-end product, o
r stated another way, because of the relatively high concentration of
cytochrome b(5) in the human testis, both the Delta 4 and the Delta 5
steroidogenic pathways can lead to testosterone production. (C) 1995 A
cademic Press, Inc.