The effect of the insulin mediator on the metabolism of androst-4-ene-3,17-dione in isolated rat hepatocytes

Abstract Insulin exerts a marked effect on hepatic steroid metabolism both in vivo and in vitro (on isolated rat hepatocytes). The mechanism by which insulin gives this action is, however, unclear. In this study, we have extracted a mediator from a hepatic membrane fraction after treatment with insulin and tested the effects of this mediator on steroid metabolism in isolated rat hepatocytes. It is seen that the mediator has a similar effect to insulin (i.e. a stimulation of enzyme activity) and that the maximum effect of the mediator is seen at physiological concentrations of insulin (10 −9 M) and at 30 min preincubation time. There appears to be a differentiation between the effects on the male-specific (6β- and 16α-hydroxylases and 17-oxosteroid oxidoreductase) and the female-specific (7α-hydroxylase and 5α-reductase) enzyme activities in that the male-specific activities appear more responsive to the mediator. This would agree with findings in vivo . It would appear, therefore, that many of the actions of insulin on hepatic steroid metabolism may be mediated by the generation of an insulin mediator, similar to that controlling mitochondrial pyruvate dehydrogenase activity, derived from the plasma membrane of the hepatocyte.