SEX-SPECIFIC AND TISSUE-SPECIFIC REGULATION OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE MESSENGER-RNA

In the present study we have investigated the effect of hypophysectomy on 11 beta HSD1 gene expression in a variety of tissues from male and female rats. Of the tissues analysed significant changes were observed only in the male and female livers, and in the female kidney. Hypophysectomy (hyper) increased hepatic message levels in the female 20-fold, and male levels rose 2-fold. Male renal 11 beta HSD1 message levels remained constant following hypophysectomy, whereas female renal 11 beta HSD1 mRNA levels increased approximately 2-fold. In intact animals hepatic 11 beta HSD1 mRNA levels are 18-fold lower in the female than the male, while renal levels are 1.4-fold higher in the male than the female. Hepatic 11 beta HSD1 levels in the female rat appear critically responsive to the pattern of growth hormone (GH) administration. Twice daily injections of GH had no significant effect on hepatic message levels in the hyper female rat, whereas constant infusions of GH, via an osmotic mini-pump produced a marked decrease. Renal 11 beta HSD1 mRNA levels were demonstrated to be under the regulation of estrogen, and 11 beta HSD1 enzyme activity in both liver and kidney correlated with the observed changes in mRNA levels. 11 beta HSD1 gene expression is thus regulated in a tissue-specific and sexually dimorphic manner.