EFFECTS OF THYROID-HORMONE (THYROXINE) AND TESTOSTERONE ON HEPATIC 11-BETA-HYDROXYSTEROID DEHYDROGENASE MESSENGER-RNA AND ACTIVITY IN PUBERTAL HYPOTHYROID MALE RATS

To investigate the effects of thyroid hormone and testosterone on 11 b eta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1), we measured ch anges in hepatic 11 beta-dehydrogenase activity and its mRNA levels in pubertal methimazole (MMI)-induced hypothyroid male rats following tr eatment with thyroxine ([T-4] 50 mu g/kg/d) or testosterone (250 mu g/ d) for 14 days. Hypothyroidism in male rats markedly reduced hepatic 1 1 beta-HSD1 mRNA levels and serum testosterone concentrations (P < .01 ). Subcutaneous injection of T-4 in the hypothyroid rats significantly (P < .01) increased hepatic 11 beta-HSD1 mRNA to approximately normal levels and simultaneously increased serum testosterone levels. Howeve r, the same daily dose of T-4 administered to castrated male hypothyro id rats for 14 days did not elevate hepatic 11 beta-HSD1 activity. Tre atment with testosterone for 14 days in castrated hypothyroid male rat s and rats without gonadectomy significantly (P < .01) increased the e nzyme activity without administration of T-4. Variations in hepatic 11 beta-HSD1 activity were demonstrated to be accompanied by changes in serum testosterone levels in the rats following alteration of the thyr oid hormone state. These results suggest that the effect of T-4 in inc reasing the subnormal 11 beta-HSD1 gene expression in hypothyroid male rats is mediated by its ability to increase testosterone production i n these rats, because in castrated hypothyroid rats, T-4 does not elev ate 11 beta-HSD1 gene expression. Copyright (C) 1998 by W.B. Saunders Company.