Sex-specific effects of growth hormone on hepatic 11beta-hydroxysteroid dehydrogenase activity and gene expression in hypothyroid rats.

To investigate the effects of growth hormone (GH) on 11beta-HSD1, we determined changes in hepatic 11beta-HSD1 activity in hypothyroid rats following treatment with subcutaneous (s.c) injection of GH for periods ranging from 24 h to 7 days. In male rats, hypothyroidism markedly reduced the hepatic 11beta-HSD1 activity and serum testosterone levels (p < 0.01). Subcutaneous injection of GH once daily to male hypothyroid rats for 48 h inhibited hepatic 11beta-HSD1 activity. However, the same daily dose of GH administered to male hypothyroid rats for 7 days, resulted in a marked increase in hepatic 11beta-HSD1 activity and gene expression (p < 0.01). Furthermore, daily s.c injections of GH to castrated male hypothyroid rats for 7 days reduced hepatic 11beta-HSD1 activity rather than inducing it, the same response seen in hypothyroid female rats. In addition, the treatment of castrated male hypothyroid rats with testosterone for 7 days significantly increased this enzyme activity (p < 0.01). The changes in hepatic 11beta-HSD1 were demonstrated to be associated with the testes in hypothyroid male rats following treatment with GH for 7 days. Moreover, the prolonged exposure to GH required to induce hepatic 11beta-HSD1 in intact hypothyroid male rats and the lack of a similar effect in castrated male hypothyroid rats suggests that this action is indirect and that it may be mediated by androgen production from Leydig cells of the testes and induced by the daily injections of GH. Treatment of hypothyroid male rats with GH at 6-h intervals, however, feminized the hepatic 11beta-HSD1 gene expression.