Normal and Recombinant Human Growth Hormone Administered by Constant Infusion Feminize Catechol Estrogen Formation by Rat Liver Microsomes*

Abstract

Human GH or recombinant DNA-derived human GH administered to normal mature male rats by constant infusion decreased hepatic 2-hydroxylation of estradiol to female levels, as measured by 3H2O release and isolation of the catechol estrogen product. PRL had no effect under the same conditions. The maximum response to GH was attained at an infusion rate of 0.02 IU/h .cntdot. kg after 5-7 days, and a significant change was observed within 1-2 days. The effect of GH was primarily on hydroxylation of C-2 of the estrogen, as demonstrated by comparative studies with estradiol labeled with 3H at C-4 or C-6,7, and appeared to be mediated by the cytochrome P-450 system of the liver microsomes. Ascorbic acid at 1 mM did not affect 2-hydroxylation significantly while protecting the catechol estrogen produced from further oxidation. The results indicate that GH has the potential to regulate estrogen metabolism in the liver and provide evidence for another component in the hypothalamic-pituitary-liver axis.