Honey, we need to talk about the membrane progestin receptors

The recent discovery of three closely related cell surface receptors that bind to progesterone and mediate its actions on various cytoplasmic signalling cascades has been heralded as a major break-through. The reason for this is all too obvious. Progesterone is an essential regulator of all major reproductive events and progestins and antiprogestins are widely used in the treatment of many different gynaecological and obstetrical disorders. The novel membrane progestin receptors (mPRalpha, beta, gamma) reportedly resemble and function as G-protein-coupled receptors and therefore are promising pharmaceutical targets. However, our studies failed to corroborate that mPRs are expressed on the cell surface, that they mediate rapid progesterone signalling events, and even that they are bona fide progestin binding moieties. While the reason for these startling opposing results remains unclear, a critical review of existing data may help to shed some light onto the controversial mPRs. Time has come to talk.