The role of cytochrome b5 in the biosynthesis of androgens by human P450c17

Arch Biochem Biophys. 1995 Mar 10;317(2):343-7. doi: 10.1006/abbi.1995.1173.


Human cytochrome b5 has a profound effect on the 17,20-lyase activities catalyzed by purified, human cytochrome P450c17. It enhances the conversion of 17 alpha-hydroxypregnenolone to dehydroepiandrosterone by 13-fold and the conversion of 17 alpha-hydroxyprogesterone to androstenedione by at least 10-fold. This latter activity is virtually undetectable in the absence of cytochrome b5. Other activities catalyzed by P450c17 include 17 alpha-hydroxylation of progesterone and pregnenolone and are much less influenced by cytochrome b5. The conversion of pregnenolone to 17 alpha-hydroxypregnenolone is increased by 2-fold, while that of progesterone to 17 alpha-hydroxyprogesterone is unchanged. These studies using purified systems suggest that cytochrome b5 plays a role in regulating the activities of P450c17 to optimize the balance between sex hormone synthesis and glucocorticoid synthesis. In particular, they indicate that in human testes which contains a high b5/P450 ratio, 17 alpha-hydroxyprogesterone can serve as an intermediate in testosterone production, rather than being a dead-end product, or stated another way, because of the relatively high concentration of cytochrome b5 in the human testis, both the delta 4 and the delta 5 steroidogenic pathways can lead to testosterone production.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 17-alpha-Hydroxypregnenolone / metabolism
  • 17-alpha-Hydroxyprogesterone
  • Aldehyde-Lyases / metabolism*
  • Androgens / biosynthesis*
  • Androstenedione / metabolism
  • Cell Membrane / enzymology
  • Cytochrome P-450 Enzyme System / metabolism*
  • Cytochromes b5 / pharmacology*
  • Dehydroepiandrosterone / metabolism
  • Escherichia coli
  • Humans
  • Hydroxyprogesterones / metabolism
  • Kinetics
  • Pregnenolone / metabolism
  • Progesterone / metabolism
  • Recombinant Proteins / metabolism
  • Steroid 17-alpha-Hydroxylase


  • Androgens
  • Hydroxyprogesterones
  • Recombinant Proteins
  • 17-alpha-Hydroxypregnenolone
  • Androstenedione
  • Dehydroepiandrosterone
  • Progesterone
  • 17-alpha-Hydroxyprogesterone
  • Pregnenolone
  • Cytochromes b5
  • Cytochrome P-450 Enzyme System
  • Steroid 17-alpha-Hydroxylase
  • Aldehyde-Lyases