Broad tissue expression of membrane progesterone receptor Alpha in normal mice

Abstract

The broad tissue distribution of membrane progesterone receptor alpha (mPRalpha) in vertebrates suggests multiple physiological functions of the receptor. Current knowledge regarding the receptor distribution, however, is largely obtained via non-histological assays. In this study, the tissue distribution of mPRalpha in mice of both sexes was described using both histological and non-histological methods. Immunohistochemical analysis revealed that abundant expression of mPRalpha was consistently detected in the cytoplasm and membrane of smooth muscles in vasculatures, gastro-intestines, and uterus. It was also observed in myoepithelial cells of mammary gland and intra-ovarian myofibroblasts. These findings suggest that mPRalpha may function as a mediator of P4 in regulating function of smooth muscles or smooth muscle-like cells in numerous physiological processes such as vasodilation, transportation of contents within luminary organs, relaxation of the uterine myometrium during pregnancy, release of oocytes, and milk secretion. In addition, strong mPRalpha expression was identified in the parietal cells of gastric glands, indicating the potential roles of P4/mPRalpha signaling in the modulation of gastric acid secretion. Surprisingly, in the testis of male mice mPRalpha was mainly seen in the nuclei, rather than cytoplasm and/or membrane, of the primary and secondary spermatocytes, suggesting a direct role of the receptor in gene regulation. Our results indicate that mPRalpha may function as a key modulator of P4 in the modulation of multiple physiological functions in normal mice.

Progesterone increases nitric oxide synthesis in human vascular endothelial cells through activation of membrane progesterone receptor-α

“…mPR␣ MEDIATES P4 UPREGULATION OF NO SYNTHESIS mPR mediating nongenomic progesterone actions in many reproductive and nonreproductive tissues (12,59), and similarly to the current results, mPR␣ is highly expressed on the plasma membranes of murine vascular endothelial cells (72). However, mPR␤ is frequently coexpressed with mPR␣ (10,11) and is a partner in mediating membrane receptor binding and physiological functions of progesterone in diverse cell types, including human myometrial cells (23), a GnRH neuronal cell line (59), breast cancer cells (44), and fish oocytes (66).…”

Progesterone reverses the mesenchymal phenotypes of basal phenotype breast cancer cells via a membrane progesterone receptor mediated pathway

“…Recently we showed that the mammary ducts of normal mice were positive for both PR and mPRα. The PR was predominantly seen in the ductal epithelium, while mPRα was mostly observed in the basal myoepithelial cells [22]. The synergistic roles of mPRα and PR in normal mammary glands remain to be explored.…”

“…The color was developed with the ImmPACT DAB kit (VECTOR Lab, Burlingame, CA, USA). Between the incubations, the slides were washed twice with 1× PBS buffer (5 minutes each) [19,22]. Two negative controls were included: (1) control slides were stained without the primary antibody; (2) control slides were incubated with a specific blocking peptide (cat# sc-50111p, Santa Cruz, CA, USA) prior to the primary antibody incubations.…”

Membrane progesterone receptors in reproduction and cancer

“…mPRs were discovered in teleost ovaries (Zhu et al, 2003b) and subsequently identified in sheep, pig, mouse, rat and human (Aparicio et al, 2011;Dressing et al, 2011;Qiu et al, 2008;Thomas et al, 2007;You et al, 2010;Zhu et al, 2003a).…”