Progesterone regulation of oxytocin receptor through non‐genomic actions

Abstract

Although high dose steroids may interfere with G protein-coupled receptor activation through disruption of cholesterol-rich plasma membrane subdomains, the mechanism of non-genomic low dose progesterone (P4) effects on oxytocin (OT) receptor activation is unknown. Low dose P4 suppressed OT-induced prostaglandin F2<alpha> secretion and inositol phosphate accumulation (Bishop et al. Endocrinology 147:937) from ovine endometrial explants, and inhibited OT binding to OT receptors (Dunlap and Stormshak, Biol Reprod 70:65). To study the mechanism of the non-genomic effects of P4 on OT receptor, we developed transfected cell lines expressing ovine OT receptor in the absence of classic progesterone steroid hormone receptors. Both transiently and stably transfected cell lines expressed ovine OT receptor at moderate to high receptor levels that coupled to activation of phopholipase C and accumulation of inositol phosphates. Low dose P4 (2.5 ng/ml) inhibited OT-stimulated inositol phosphate accumulation in the transfected cell lines. Of interest, the ability of P4 to suppress OT-induced inositol phosphate accumulation in transfected cells varied with OT receptor expression levels, suggesting an allosteric effect of low dose P4 on ovine OT receptor function.