Non-genomic progesterone receptors in the mammalian ovary: some unresolved issues

Abstract

In addition to their well-documented genomic effects, steroid hormones may also exert actions that are: (i) rapid, (ii) insensitive to inhibitors of transcription, (iii) mimicked by steroids coupled to cell membrane-impermeant molecules, and (iv) demonstrable in cells that do not express the classic genomic progesterone receptor (gPR). Such 'non-genomic' effects have been described for all the major classes of steroids (progesterone, oestrogens, androgens and corticoids), as well as for thyroid hormones, retinoids and vitamin D(3). Rapid, membrane-mediated effects of progesterone have been studied most intensively in human spermatozoa and in the Xenopus oocyte. However, similar non-genomic actions of progesterone and other steroids have now been described in a wide variety of different tissues in many species. The first putative membrane steroid receptor to be cloned was that for the pig membrane progesterone receptor (mPR). Subsequently, similar genes were cloned from rats and cattle, and two related mPRs have been described in humans. Despite accumulating evidence for cell-surface membrane actions of steroids, a number of uncertainties remain as to the properties and identity of such 'receptors' and their cellular actions. Furthermore, some rapid steroid effects may be mediated through membrane-associated 'classical' steroid receptors, and steroid receptors may be capable of activating other signalling pathways non-classically. This review focuses on some of these unresolved issues, taking as its model the actions of progesterone in the mammalian ovary.