Co-induction of 17 alpha-hydroxylase and C-17,20-lyase activities in primary cultures of bovine adrenocortical cells in response to ACTH treatment.
Bovine adrenocortical cells in primary culture were used to examine the trophic effect of ACTH on the induction of the 17 alpha-hydroxylase and C-17,20-lyase activities. The addition of exogenous pregnenolone to bovine adrenal microsomes showed the appearance of 17 alpha-hydroxy-pregnenolone before the formation of dehydroepiandrosterone. The same sequence of activities was evident in postmitochondrial supernate from bovine adrenocortical cells cultured 36 h in the presence of 1 microM ACTH but not in postmitochondrial supernate from control cells. In another study, bovine adrenocortical cells were cultured for 36 h after which 30 microM 17 alpha-hydroxypregnenolone was added to the medium and the incubation continued 1 h; there was a 4-fold increase in androgen content in the media from ACTH-treated cells over controls. Measurement of the 17 alpha-hydroxylase and C-17,20-lyase reactions in postmitochondrial supernate from cells cultured 0-72 h in the presence of ACTH or 1 mM dibutyryl cAMP showed concomitant increases in the two activities and both activities were inhibited by the same compounds known to inhibit 17 alpha-hydroxylase activity. These observations support the concept of the co-induction of 17 alpha-hydroxylase and C-17,20-lyase activities in response to ACTH; results in keeping with previous studies indicating that the two activities are catalyzed by a single gene product, the polypeptide chain P-45017a.
McCarthy
J L
JL
Department of Biology, Southern Methodist University, Dallas, TX 75275.
Waterman
M R
MR
D006907:17-alpha-Hydroxypregnenolone / Q000096:biosynthesis / Q000494:pharmacology; D000302:Adrenal Cortex / Q000187:drug effects / Q000201:enzymology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000446:Aldehyde-Lyases / Q000096:biosynthesis*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003687:Dehydroepiandrosterone / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology; D011284:Pregnenolone / Q000494:pharmacology; D013254:Steroid 17-alpha-Hydroxylase / Q000096:biosynthesis*; D013250:Steroid Hydroxylases / Q000096:biosynthesis*
D006907:17-alpha-Hydroxypregnenolone; D003687:Dehydroepiandrosterone; D003994:Bucladesine; D011284:Pregnenolone; D000324:Adrenocorticotropic Hormone; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D013254:Steroid 17-alpha-Hydroxylase; D000446:Aldehyde-Lyases