Regulation of steroid 17 alpha-hydroxylase in adrenocortical cells in culture.
The regulation of steroid 17 alpha-hydroxylase in human and bovine adrenocortical cells in culture is reviewed. It is shown that (i) the long-term growth and cloning of normal human fetal adrenocortical cells in culture is feasible; (ii) the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) is an effective mitogen in both clonal cultures and non-clonal early cultures of human adrenocortical cells, and shows a selective action in promoting adrenocortical cell growth and inhibiting fibroblast growth; (iii) the key steroidogenic enzymes, 17 alpha-hydroxylase and 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), are under dual regulation by the cyclic AMP and protein kinase C second messenger systems; (iv) for 17 alpha-hydroxylase, this dual regulation is mediated by changes in 17 alpha-hydroxylase mRNA levels; (v) bovine adrenocortical cells can be transfected with SV40 T antigen, producing lines with elevated differentiated functions, including stabilized high expression of 17 alpha-hydroxylase; (vi) human adrenocortical cells can also be transfected with SV40 large T antigen, giving rise to functional cell lines which may be useful in future studies of 17 alpha-hydroxylase regulation.
Hornsby
P J
PJ
Department of Cell and Molecular Biology, Medical College of Georgia, Augusta 30912.
D000302:Adrenal Cortex / Q000187:drug effects / Q000201:enzymology*; D000728:Androgens / Q000096:biosynthesis; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002999:Clone Cells; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D005333:Fetus; D006801:Humans; D007700:Kinetics; D015290:Second Messenger Systems; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism*; D013250:Steroid Hydroxylases / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000728:Androgens; D005576:Colforsin; D003687:Dehydroepiandrosterone; D000242:Cyclic AMP; D013250:Steroid Hydroxylases; D013254:Steroid 17-alpha-Hydroxylase; D013755:Tetradecanoylphorbol Acetate