Interactions of insulin, thyroxine and dexamethasone with growth hormone in the control of steroid metabolism by isolated rat hepatocytes.
In vivo studies have established that continuous infusion of male rats with growth hormone (GH) results in the feminisation of hepatic steroid metabolism. In this study, however, no feminising effects were observed in response to GH treatment alone in isolated hepatocytes. Combined incubations with insulin and GH or with dexamethasone and GH showed that GH antagonised the stimulatory effects of insulin and dexamethasone respectively. Pretreatment of hepatocytes over 30 min with thyroxine and GH also resulted in a decrease in enzyme activity as compared to the response with thyroxine alone. Thus no feminisation effects were seen with any of the combinations of hormones noted above. Preincubation of hepatocytes with dexamethasone, thyroxine and GH, however, resulted in the expression of the feminisation effect noted in vivo. It therefore appears from this study that dexamethasone and thyroxine may play a permissive role in mediating the feminising effects of GH in isolated hepatocytes, and that GH may be interacting with these hormones in vivo to produce such effects.
Gulati
P
P
Department of Pharmacology, The University, Glasgow, U.K.
Skett
P
P
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004347:Drug Interactions; D013006:Growth Hormone / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000378:metabolism; D013256:Steroids / Q000378:metabolism*; D013974:Thyroxine / Q000494:pharmacology*
D007328:Insulin; D013256:Steroids; D003907:Dexamethasone; D013006:Growth Hormone; D003577:Cytochrome P-450 Enzyme System; D015067:17-Hydroxysteroid Dehydrogenases; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D039181:Steroid 16-alpha-Hydroxylase; C022657:steroid hormone 6-beta-hydroxylase; C029009:steroid hormone 7-alpha-hydroxylase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D013974:Thyroxine