Regulation of steroid hydroxylase gene expression and steroid hormone biosynthesis.

In our test system, the action of glucagon o n steroid oxidation follows a dose-response relationship similar to its actions on diacylglycerol generation and not on cyclic AMP generation [ 171. The fact that it does not act via activation of adenylate cyclase and generation of cyclic AMP was proved by the usc of I-N-a-trinitrophenylhistidine12-homoarginine glucagon (TH)-glucagon, an analogue of the natural hormone, which activates polyphosphoinositide hydrolysis, but not adenylate cyclase. TH-glucagon inhibited steroid oxidation in the same manner as glucagon itself [ 1 I]. THglucagon does not show the U-shaped dose-response curve of glucagon for its action on steroid metabolism, but reached a maximum effect at lo-’ M, which is sustained up to lo-’ M [ 1 11. This is identical to the effects of TH-glucagon on diacylglycerol generation in hepatocytes [ 171. The mechanism of action of growth hormone is at present unclear and, because of the requirement of growth hormone action for adrenal and thyroid hormones, may be more difficult to decipher. In summary, insulin and glucagon have direct, independent effects on hepatic mixed-function oxidases via generation of an insulin mediator and activation of protein kinase C, respectively. Growth hormone can counteract the effect of insulin and has the ‘feminizing’ effect observed in vivo directly on isolated hepatocytes in the presence of adrenal and thyroid hormones (perhaps acting in a permissive manner).