Sexually differentiated expression of genes encoding the P4502C cytochromes in rat liver--a model system for studying the action of growth hormone.

Growth hormone (GH) is an important regulator of the expression of several members of the cytochrome P4502C subfamily in rat liver. The sexually differentiated pattern of secretion of GH in the adult rat leads to a sex-dependent expression of the GH-regulated P450 genes. The continuous presence of GH in serum is characteristic of the female rat and maintains a high expression of P4502C12 while it represses P4502C11 expression. By contrast, the P4502C11 form is induced by the intermittent, male characteristic, GH pattern. A direct effect of GH on the hepatocyte is evident from studies using primary adult rat hepatocytes in culture and, furthermore, the regulation has been shown to occur at the level of transcription. How the hepatocyte can distinguish between different patterns of GH exposure is as yet unresolved and neither are the signalling pathway(s) that are involved in the mediation of the GH effects known. However, a cascade of phosphorylations starting at the receptor are triggered. Our data indicate that protein kinase C activity is necessary for the GH effect on P4502C12 and that some other kinase, sensitive to staurosporine, is a determining transducer. The dual regulation by GH of the genes encoding P4502C11 and P4502C12 and the GH responsiveness of primary hepatocytes offer versatile tools for studies aimed at understanding the cellular and molecular mechanisms of GH action.