Over long periods of growth in culture, bovine adrenocortical cells lose the ability to express the steroid hydroxylase genes. For 17αhydroxylase, 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 11βhydroxylase) appear to undergo phenotypic switching like 17ßhydroxylase. The loss of expression of these genes appears to be more rapid, but there are differences in the requirements of 21-hydroxylase and 11βhydroxylase versus 17ßhydroxylase for induction by cyclic AMP; additionally, growth of cells in extracellular matrix Matrigel was required for expression of 21-hydroxylase and 11βhydroxylase 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.
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