Cellular localization of 11 beta-hydroxysteroid dehydrogenase 2 gene expression in the ovine adrenal gland

The cellular localization of 11 beta-hydroxysteroid dehydrogenase 2 (11 beta-HSD2) gene expression in the ovine adrenal gland was determined by in situ hybridization histochemistry. 11 beta-HSD2 mRNA was localized exclusively to the adrenal cortex of the adult sheep, and within the cortex the mRNA was highly expressed in the zona fasciculata and zona reticularis with relatively low expression in the zona glomerulosa. Radiometric conversion assay using adrenal cortical tissues revealed extremely high levels of 11 beta-HSD activity which was characteristic of 11 beta-HSD2 in that it was NAD-dependent and displayed a Km for cortisol of 41 +/- 4 nM. This indicates that 11 beta-HSD2 mRNA within the ovine adrenal gland is translated and functional with respect to enzymatic activity. In marked contrast, 11 beta-HSD1 mRNA was undetectable in either the cortex or medulla of adult sheep adrenal glands. In conclusion, we have demonstrated, for the first time, the zonal localization of 11 beta-HSD2 mRNA and the presence of 11 beta-HSD2 activity in the adult sheep adrenal cortex. The adrenal 11 beta-HSD2 may function to (1) regulate the rate of cortisol secretion by adrenocortical cells; (2) protect these cells from high levels of locally produced glucocorticoids; and/or (3) provide an important source of circulating cortisone, which can be activated by the action of 11 beta-HSD1 reductase in organs such as the liver.