SEX-SPECIFIC EFFECTS OF GROWTH-HORMONE ON HEPATIC 11-BETA-HYDROXYSTEROID DEHYDROGENASE-ACTIVITY AND GENE-EXPRESSION IN HYPOTHYROID RATS

To investigate the effects of growth hormone (GH) on 11 beta-HSD1, we determined changes in hepatic 11 beta-HSD1 activity in hypothyroid rat s following treatment with subcutaneous (s.c) injection of GH for peri ods ranging from 24 h to 7 days. In male rats, hypothyroidism markedly reduced the hepatic 11 beta-HSD1 activity and serum testosterone leve ls (p < 0.01). Subcutaneous injection of GH once daily to male hypothy roid rats for 48 h inhibited hepatic 11 beta-HSD1 activity. However, t he same daily dose of GH administered to male hypothyroid rats for 7 d ays, resulted in a marked increase in hepatic 11 beta-HSD1 activity an d gene expression (p < 0.01). Furthermore, daily s.c injections of GH to castrated male hypothyroid rats for 7 days reduced hepatic 11 beta- HSD1 activity rather than inducing it, the same response seen in hypot hyroid female rats. In addition, the treatment of castrated male hypot hyroid rats with testosterone for 7 days significantly increased this enzyme activity (p < 0.01). The changes in hepatic II beta-HSD1 were d emonstrated to be associated with the testes in hypothyroid male rats following treatment with GH for 7 days. Moreover, the prolonged exposu re to GH required to induce hepatic 11 beta-HSD1 in intact hypothyroid male rats and the lack of a similar effect in castrated male hypothyr oid rats suggests that this action is indirect and that it may be medi ated by androgen production from Leydig cells of the testes and induce d by the daily injections of GH. Treatment of hypothyroid male rats wi th GH at 6-h intervals, however, feminized the hepatic 11 beta-HSD1 ge ne expression.