Regulation of 11beta-hydroxysteroid dehydrogenase type II expression in the renal epithelial cells

The regulation of 11beta-hydroxysteroid dehydrogenase type II (11betaHSD2) expression at the level of specific mRNA and 11betaHSD2 protein was investigated in primary culture of renal epithelial cells of the rat. It has been shown that treatment of the SE cells with adenylyl cyclase activator, forskolin, known to stimulate the protein kinase A (PKA) pathway, resulted in an increase in 11betaHSD2 mRNA content in these cells. Semi-quantitative RT-PCR revealed that the effect of forskolin was attenuated by the addition of phorbol ester, tetradecanoyl phorbol acetate (TPA), an activator of the protein kinase C (PKC) pathway, whereas TPA on its own slightly reduced the basal level of 11betaHSD2 expression judging from the content of specific mRNA. Measurements of [35S]-methionine incorporation into immunoprecipitable 11betaHSD2 revealed an increased synthesis of this protein in renal epithelial cells treated with forskolin. Phorbol ester TPA markedly reduced the effect of forskolin on the synthesis of 11betaHSD2 and attenuated the basal level of synthesis of this protein. It is concluded that in renal epithelial cells in primary culture, stimulation of PKA pathway results in the induction of 11betaHSD2 both at a specific mRNA and at a protein level and that this effect is markedly reduced by activation of PKC pathway.