Regulation of steroid hydroxylases in normal and SV40 T antigen-transfected bovine adrenocortical cells in long-term culture.
Over long periods of growth in culture, bovine adrenocortical cells lose the ability to express the steroid hydroxylase genes. For 17 alpha-hydroxylase, cells show a stochastic pattern of phenotypic switching from a state in which they express this gene in response to cyclic AMP to a state in which the gene is no longer inducible. Introducing SV40 T antigen into bovine adrenocortical cells greatly increases their replicative potential; steroid hydroxylase expression in these clones resembles that of the precursor cells before transfection. The other steroid hydroxylases (21-hydroxylase and 11 beta-hydroxylase) appear to undergo phenotypic switching like 17 alpha-hydroxylase. The loss of expression of these genes appears to be more rapid, but there are differences in the requirements of 21-hydroxylase and 11 beta-hydroxylase versus 17 alpha-hydroxylase for induction by cyclic AMP; additionally, growth of cells in extracellular matrix Matrigel was required for expression of 21-hydroxylase and 11 beta-hydroxylase in long-term cultures of either normal or SV40 T antigen-transfected cells. Understanding the molecular basis for the phenotypic switching of steroid hydroxylases that occurs in bovine adrenocortical cells may elucidate mechanisms for cellular senescence and for maintenance of tissue-specific functions during long-term growth in culture.
Hornsby
P J
PJ
Department of Cell and Molecular Biology, Medical College of Georgia, Augusta 30912.
D000302:Adrenal Cortex / Q000166:cytology* / Q000201:enzymology / Q000502:physiology; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002642:Chick Embryo; D015870:Gene Expression; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D014162:Transfection
D000952:Antigens, Polyomavirus Transforming; D013250:Steroid Hydroxylases