Membrane progestin receptors α and γ in renal epithelium

Sex hormones have broader effects than regulating reproductive functions. Recent identification of membrane progestin receptors expressed in kidney prompted us to investigate their putative involvement in the renal effects of this hormone. We first focused our investigations on mPRα and γ by analyzing three parameters 1/ their distribution along the mouse nephron and their subcellular location in native kidney, 2/ the ability of progesterone to stimulate ERK pathway and/or Ca2+ release from internal stores in native kidney structures and 3/ the cellular localization of mPRα and its molecular determinants in heterologous expression system. We observed that 1/ mPRα expression is restricted to proximal tubules of both male and female mice whereas mPRγ exhibits a much broader expression all along the nephron except the glomerulus, 2/ mPRα and γ are not localized at the plasma membrane in native kidney, 3/ this expression does not permit either progesterone-induced ERK phosphorylation or Ca2+ release and 4/ in HEK transfected cells, mPRα localizes in the endoplasmic reticulum (ER) due to a C-terminal ER retention motif (− KXX). Therefore, we have characterized mPRs in kidney but their role in renal physiology remains to be elucidated.