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.
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ABSTRACT: We have previously shown that progesterone receptor (PR) is expressed in the mesothelium of the chick oviduct and ovary and in the smooth muscle cells of the oviduct and the bursa of Fabricius. Here, we investigated the presence of PR in different parts of the peritoneum and abdominal organs using an immunohistochemical staining based on monoclonal antibodies against chicken PR. In 4-week-old sexually immature chicks, PR expression was located in the mesothelial cells of different parts of the peritoneum, in a thin layer of muscle cells of the ileum and throughout the muscle tissue of the colon and cloaca. In chicks of the same age treated with estrogen, PR was demonstrated similarly in the peritoneum and in the smooth muscle cells of the ileum, colon and cloaca. Using 25-week-old mature chickens, PR was also detected in identical tissues. Immunoblotting of the cloacal cytosol revealed the B form, but no A form of PR, both of which were found in the oviduct samples. Muscle cells of the duodenum and jejunum were not found to contain PR. Estrogen treatment was not needed to stimulate the production of PR in any of the tissues examined. We therefore conclude that the B form of PR is constitutively expressed in the mesothelial cells in different parts of the peritoneum and also in the smooth muscle cells of the ileum, colon and cloaca.Journal of Steroid Biochemistry 02/1989; 34(1-6):345-9.
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ABSTRACT: Age-related impaired wound healing leads to substantial morbidity and mortality along with a large financial burden to health services. There is accumulating evidence that the tissue damage associated with chronic wounds is initiated and propagated by an inappropriately excessive inflammatory response. Research on age-related impaired wound healing suggests that the decline in sex steroid hormones with age may have a substantial influence on the inflammatory response in vivo. Topical and systemic estrogen treatments have shown an increased rate of healing by reducing inflammation, however the underlying mechanisms are little understood. In vitro studies also suggest progesterone may play a role in modulating inflammation. Macrophages are essential mediators of inflammation and wound healing. Macrophages can be activated in a classical or alternative manner in parallel with the T(H)1/T(H)2 dichotomy, respectively. Using a murine incisional wound healing model this study was carried out to investigate the roles of estrogen and progesterone on macrophage activation during the wound healing response. Our findings suggest with a reduction of steroid hormones following ovariectomy, alternatively activated macrophage markers (Fizz1 and Ym1) were reduced, with this effect being reversed with the administration of estrogen or progesterone; suggesting that with the reduction of steroid hormones macrophages are activated in a classical manner, promoting inflammation, whereas estrogen or progesterone are contributing toward macrophage activation in an alternative manner, driving wound repair, angiogenesis, and remodeling.Wound Repair and Regeneration 02/2009; 17(1):42-50. · 2.76 Impact Factor
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ABSTRACT: Classically, progesterone has been thought to act only through the well-known genomic pathway involving hormone binding to nuclear receptors (nPR) and subsequent modulation of gene expression. However, there is increasing evidence for rapid, nongenomic effects of progesterone in a variety of tissues in mammals, and it seems likely that a membrane PR (mPR) is causing these events. The objective of this study was to isolate and characterize an ovine mPR distinct from the nPR. A cDNA clone was isolated from ovine genomic DNA by PCR. The ovine mPR is a 350-amino acid protein that, based on computer hydrophobicity analysis, possesses seven transmembrane domains and is distinct from the nPR. Message for the ovine mPR was detected in hypothalamus, pituitary, uterus, ovary, and corpus luteum by RT-PCR. In CHO cells that overexpressed a mPR-green fluorescent protein fusion protein, the ovine mPR was localized to the endoplasmic reticulum and not the plasma membrane. Specific binding of 3H-progesterone to membrane fractions was demonstrated in CHO cells that expressed the ovine mPR but not in nontransfected cells. Furthermore, progesterone and 17 alpha-hydroxy-progesterone stimulated intracellular Ca2+ mobilization in CHO cells that expressed ovine mPR in Ca2+-free medium (P < 0.05) but not in CHO cells transfected with empty vector. This rise in intracellular Ca2+ is believed to be from the endoplasmic reticulum as intracellular Ca2+ mobilization is absent when mPR transfected cells are first treated with thapsigargin to deplete Ca2+ stores from the endoplasmic reticulum. Isolation, identification, tissue distribution, cellular localization, steroid binding, and a functional response for a unique intracellular mPR in the sheep are presented.Endocrinology 10/2006; 147(9):4151-9. · 4.72 Impact Factor