Membrane progesterone receptor expression in mammalian tissues: A review of regulation and physiological implications

Abstract

The recent discovery of a novel, membrane localized progestin receptor (mPR) unrelated to the classical progesterone receptor (PR) in fishes and its subsequent identification in mammals suggests a potential mediator of non-traditional progestin actions, particularly in tissues where PR is absent. While early studies on mPR focused on final oocyte maturation in fishes, more current studies have examined mPRs in multiple mammalian systems in both reproductive and nonreproductive tissues as well as in diseased tissues. Here we review the current data on mPR in mammalian systems including male and female reproductive tracts, liver, neuroendocrine tissues, the immune system and breast and ovarian cancer. We also provide new data demonstrating mPR expression in the RAW 264.7 immune cell line and bone marrow-derived macrophages as well as mPR expression and downstream gene regulation in ovarian cancer cells.

Signaling Pathways in Leiomyoma: Understanding Pathobiology and Implications for Therapy

“…Both are transcribed from the same gene with PRB being larger by 164 amino acids (52). Genes for membrane progesterone receptors (mPR) were initially identified in fish and later in human and are present in three isoforms; mPRα, mPRβ and mPRγ (53,54). Although these membrane receptors are expressed in uterus (54), there are no published studies to address their expression or role in uterine leiomyoma.…”

Membrane progesterone receptors in human regulatory T cells: a reality in pregnancy

“…10 In the quest for a novel agent in PTB treatment, progesterone emerges as a good candidate due to its immunomodulatory action. 11 Although the exact mechanism of its immunomodulatory role is still unknown, reports demonstrate its rapid effects on human T cells. 2,12 The extranuclear activity of progestins was identified to be mediated by an alternative membrane-localised progesterone receptor (mPR), which may be responsible for the rapid cell activation prompted by progesterone 11,13 and progesterone interaction with the immune system.…”

“…11 Although the exact mechanism of its immunomodulatory role is still unknown, reports demonstrate its rapid effects on human T cells. 2,12 The extranuclear activity of progestins was identified to be mediated by an alternative membrane-localised progesterone receptor (mPR), which may be responsible for the rapid cell activation prompted by progesterone 11,13 and progesterone interaction with the immune system. 14 The function of one of these receptors, mPRa, has been investigated 15 but its expression on specific subsets of immune cells has hardly been demonstrated.…”

Progesterone Resistance and Targeting the Progesterone Receptors: A Therapeutic Approach to Endometriosis

“…Outside of the predicted protection from catamenial exacerbation of epileptic seizures and premenstrual dysphoric disorder by neurosteroids (Biagini et al, 2010), the non-genomic effects of progesterone in reproductive function in the female human have been less well characterised. Several other reported progesterone receptors (mPR, PGRMC1 and CatSper, for instance) have also been touted to contribute to the non-genomic effects of progesterone (Dressing et al, 2011;Gellersen et al, 2009;Lishko et al, 2011;Zhu et al, 2003). Based on expression data and some functional characterisation both mPR and PGRMC1 may have a role in reproductive function and are speculated to regulate implantation and myometrial contractility.…”