Sex- and tissue- specific regulation of 11β-hydroxysteroid dehydrogenase mRNA

Abstract

In the present study we have investigated the effect of hypophysectomy on 11βHSD1 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 (hypox) increased hepatic message levels in the female 20-fold, and male levels rose 2-fold. Male renal 11βHSD1 message levels remained constant following hypophysectomy, whereas female renal 11βHSD1 mRNA levels increased approximately 2-fold. In intact animals hepatic 11βHSD1 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 11βHSD1 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 hypox female rat, whereas constant infusions of GH, via an osmotic mini-pump produced a marked decrease. Renal 11βHSD1 mRNA levels were demonstrated to be under the regulation of estrogen, and 11βHSD1 enzyme activity in both liver and kidney correlated with the observed changes in mRNA levels. 11βHSD1 gene expression is thus regulated in a tissue-specific and sexually dimorphic manner.