Skip to main content

Advertisement

SpringerLink
Log in

Broad tissue expression of membrane progesterone receptor Alpha in normal mice

  • Original Paper
  • Published:
Journal of Molecular Histology Aims and scope Submit manuscript

Abstract

The broad tissue distribution of membrane progesterone receptor alpha (mPRα) 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 mPRα in mice of both sexes was described using both histological and non-histological methods. Immunohistochemical analysis revealed that abundant expression of mPRα 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 mPRα 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 mPRα expression was identified in the parietal cells of gastric glands, indicating the potential roles of P4/mPRα signaling in the modulation of gastric acid secretion. Surprisingly, in the testis of male mice mPRα 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 mPRα may function as a key modulator of P4 in the modulation of multiple physiological functions in normal mice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Ashley RL, Clay CM, Farmerie TA, Niswender GD, Nett TM (2006) Cloning and characterization of an ovine intracellular seven transmembrane receptor for progesterone that mediates calcium mobilization. Endocrinology 147:4151–4159

    Article  CAS  PubMed  Google Scholar 

  • Bouman A, Heineman MJ, Faas MM (2005) Sex hormones and the immune response in humans. Hum Reprod Update 11:411–423

    Article  CAS  PubMed  Google Scholar 

  • Butts CL, Shukair SA, Duncan KM, Bowers E, Horn C, Belyavskaya E, Tonelli L, Sternberg EM (2007) Progesterone inhibits mature rat dendritic cells in a receptor-mediated fashion. Int Immunol 19:287–296

    Article  CAS  PubMed  Google Scholar 

  • Cheng L, Pricolo V, Biancani P, Behar J (2008) Over expression of progesterone receptor B increases sensitivity of human colon muscle cells to progesterone. Am J Physiol Gastrointest Liver Physiol 295:G493–G502

    Article  CAS  PubMed  Google Scholar 

  • Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T (1998) Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group. N Engl J Med 339:285–291

    Article  CAS  PubMed  Google Scholar 

  • D’Eon T, Braun B (2002) The roles of estrogen and progesterone in regulating carbohydrate and fat utilization at rest and during exercise. J Womens Health Gend Based Med 11:225–237

    Article  PubMed  Google Scholar 

  • Dosiou C, Hamilton AE, Pang Y, Overgaard MT, Tulac S, Dong J, Thomas P, Giudice LC (2008) Expression of membrane progesterone receptors on human T lymphocytes and Jurkat cells and activation of G-proteins by progesterone. J Endocrinol 196:67–77

    Article  CAS  PubMed  Google Scholar 

  • Dressing GE, Thomas P (2007) Identification of membrane progestin receptors in human breast cancer cell lines and biopsies and their potential involvement in breast cancer. Steroids 72:111–116

    Article  CAS  PubMed  Google Scholar 

  • Eliakim R, Abulafia O, Sherer DM (2000) Estrogen, progesterone and the gastrointestinal tract. J Reprod Med 45:781–788

    CAS  PubMed  Google Scholar 

  • Falkenstein E, Meyer C, Eisen C, Scriba PC, Wehling M (1996) Full-length cDNA sequence of a progesterone membrane-binding protein from porcine vascular smooth muscle cells. Biochem Biophys Res Commun 229:86–89

    Article  CAS  PubMed  Google Scholar 

  • Falkenstein E, Tillmann HC, Christ M, Feuring M, Wehling M (2000) Multiple actions of steroid hormones—a focus on rapid, nongenomic effects. Pharmacol Rev 52:513–556

    CAS  PubMed  Google Scholar 

  • Fernandes MS, Pierron V, Michalovich D, Astle S, Thornton S, Peltoketo H, Lam EW, Gellersen B, Huhtaniemi I, Allen J et al (2005) Regulated expression of putative membrane progestin receptor homologues in human endometrium and gestational tissues. J Endocrinol 187:89–101

    Article  CAS  PubMed  Google Scholar 

  • Fernandez-Capetillo O, Mahadevaiah SK, Celeste A, Romanienko PJ, Camerini-Otero RD, Bonner WM, Manova K, Burgoyne P, Nussenzweig A (2003) H2AX is required for chromatin remodeling and inactivation of sex chromosomes in male mouse meiosis. Dev Cell 4:497–508

    Article  CAS  PubMed  Google Scholar 

  • Frye CA, Sumida K, Lydon JP, O’Malley BW, Pfaff DW (2006) Mid-aged and aged wild-type and progestin receptor knockout (PRKO) mice demonstrate rapid progesterone and 3alpha, 5alpha-THP-facilitated lordosis. Psychopharmacology (Berl) 185:423–432

    Article  CAS  Google Scholar 

  • Gellersen B, Fernandes MS, Brosens JJ (2009) Non-genomic progesterone actions in female reproduction. Hum Reprod Update 15:119–138

    Article  CAS  PubMed  Google Scholar 

  • Gomez F, Ruiz P, Briceno F, Lopez R, Michan A (1998) Treatment with progesterone analogues decreases macrophage Fcgamma receptors expression. Clin Immunol Immunopathol 89:231–239

    Article  CAS  PubMed  Google Scholar 

  • Graham JD, Clarke CL (1997) Physiological action of progesterone in target tissues. Endocr Rev 18:502–519

    Article  CAS  PubMed  Google Scholar 

  • Hens JR, Wilson KM, Dann P, Chen X, Horowitz MC, Wysolmerski JJ (2005) TOPGAL mice show that the canonical Wnt signaling pathway is active during bone development and growth and is activated by mechanical loading in vitro. J Bone Miner Res 20:1103–1113

    Article  CAS  PubMed  Google Scholar 

  • Kalo-Klein A, Witkin SS (1989) Candida albicans: cellular immune system interactions during different stages of the menstrual cycle. Am J Obstet Gynecol 161:1132–1136

    CAS  PubMed  Google Scholar 

  • Kariagina A, Aupperlee MD, Haslam SZ (2007) Progesterone receptor isoforms and proliferation in the rat mammary gland during development. Endocrinology 148:2723–2736

    Article  CAS  PubMed  Google Scholar 

  • Karteris E, Zervou S, Pang Y, Dong J, Hillhouse EW, Randeva HS, Thomas P (2006) Progesterone signaling in human myometrium through two novel membrane G protein-coupled receptors: potential role in functional progesterone withdrawal at term. Mol Endocrinol 20:1519–1534

    Article  CAS  PubMed  Google Scholar 

  • Kastner P, Krust A, Turcotte B, Stropp U, Tora L, Gronemeyer H, Chambon P (1990) Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. EMBO J 9:1603–1614

    CAS  PubMed  Google Scholar 

  • Kazeto Y, Goto-Kazeto R, Thomas P, Trant JM (2005) Molecular characterization of three forms of putative membrane-bound progestin receptors and their tissue-distribution in channel catfish, Ictalurus punctatus. J Mol Endocrinol 34:781–791

    Article  CAS  PubMed  Google Scholar 

  • Kim S, Namekawa SH, Niswander LM, Ward JO, Lee JT, Bardwell VJ, Zarkower D (2007) A mammal-specific Doublesex homolog associates with male sex chromatin and is required for male meiosis. PLoS Genet 3:e62

    Article  PubMed  Google Scholar 

  • Ko C, Gieske MC, Al-Alem L, Hahn Y, Su W, Gong MC, Iglarz M, Koo Y (2006) Endothelin-2 in ovarian follicle rupture. Endocrinology 147:1770–1779

    Article  CAS  PubMed  Google Scholar 

  • Losel R, Wehling M (2003) Nongenomic actions of steroid hormones. Nat Rev Mol Cell Biol 4:46–56

    Article  PubMed  Google Scholar 

  • Losel R, Breiter S, Seyfert M, Wehling M, Falkenstein E (2005) Classic and non-classic progesterone receptors are both expressed in human spermatozoa. Horm Metab Res 37:10–14

    Article  CAS  PubMed  Google Scholar 

  • Mendelsohn ME, Karas RH (1999) The protective effects of estrogen on the cardiovascular system. N Engl J Med 340:1801–1811

    Article  CAS  PubMed  Google Scholar 

  • Michaletz-Onody PA (1992) Peptic ulcer disease in pregnancy. Gastroenterol Clin North Am 21:817–826

    CAS  PubMed  Google Scholar 

  • Minshall RD, Pavcnik D, Browne DL, Hermsmeyer K (2002) Nongenomic vasodilator action of progesterone on primate coronary arteries. J Appl Physiol 92:701–708

    CAS  PubMed  Google Scholar 

  • Miyaura H, Iwata M (2002) Direct and indirect inhibition of Th1 development by progesterone and glucocorticoids. J Immunol 168:1087–1094

    CAS  PubMed  Google Scholar 

  • Nelson JL, Ostensen M (1997) Pregnancy and rheumatoid arthritis. Rheum Dis Clin North Am 23:195–212

    Article  CAS  PubMed  Google Scholar 

  • Oettel M, Mukhopadhyay AK (2004) Progesterone: the forgotten hormone in men? Aging Male 7:236–257

    Article  CAS  PubMed  Google Scholar 

  • Pace MC, Thomas P (2005) Activation of a pertussis toxin-sensitive, inhibitory G-protein is necessary for steroid-mediated oocyte maturation in spotted seatrout. Dev Biol 285:70–79

    Article  CAS  PubMed  Google Scholar 

  • Quinkler M, Bumke-Vogt C, Meyer B, Bahr V, Oelkers W, Diederich S (2003) The human kidney is a progesterone-metabolizing and androgen-producing organ. J Clin Endocrinol Metab 88:2803–2809

    Article  CAS  PubMed  Google Scholar 

  • Richards JS (1980) Maturation of ovarian follicles: actions and interactions of pituitary and ovarian hormones on follicular cell differentiation. Physiol Rev 60:51–89

    CAS  PubMed  Google Scholar 

  • Routley CE, Ashcroft GS (2009) Effect of estrogen and progesterone on macrophage activation during wound healing. Wound Repair Regen 17:42–50

    Article  PubMed  Google Scholar 

  • Salomaa S, Pekki A, Sannisto T, Ylikomi T, Tuohimaa P (1989) Progesterone receptor is constitutively expressed in chicken intestinal mesothelium and smooth muscle. J Steroid Biochem 34:345–349

    Article  CAS  PubMed  Google Scholar 

  • Schuffner AA, Bastiaan HS, Duran HE, Lin ZY, Morshedi M, Franken DR, Oehninger S (2002) Zona pellucida-induced acrosome reaction in human sperm: dependency on activation of pertussis toxin-sensitive G(i) protein and extracellular calcium, and priming effect of progesterone and follicular fluid. Mol Hum Reprod 8:722–727

    Article  CAS  PubMed  Google Scholar 

  • Simoncini T, Genazzani AR (2000) Direct vascular effects of estrogens and selective estrogen receptor modulators. Curr Opin Obstet Gynecol 12:181–187

    Article  CAS  PubMed  Google Scholar 

  • Smith R (2007) Parturition. N Engl J Med 356:271–283

    Article  CAS  PubMed  Google Scholar 

  • Tesarik J, Moos J, Mendoza C (1993) Stimulation of protein tyrosine phosphorylation by a progesterone receptor on the cell surface of human sperm. Endocrinology 133:328–335

    Article  CAS  PubMed  Google Scholar 

  • Thomas P (2004) Discovery of a new family of membrane progesterone receptors in vertebrates and detection of the alpha and beta subtypes in mouse brain, testis and uterus. Med Chem Res 13:202–209

    Article  CAS  Google Scholar 

  • Thomas P (2008) Characteristics of membrane progestin receptor alpha (mPRalpha) and progesterone membrane receptor component 1 (PGMRC1) and their roles in mediating rapid progestin actions. Front Neuroendocrinol 29:292–312

    Article  CAS  PubMed  Google Scholar 

  • Thomas P, Tubbs C, Detweiler C, Das S, Ford L, Breckenridge-Miller D (2005) Binding characteristics, hormonal regulation and identity of the sperm membrane progestin receptor in Atlantic croaker. Steroids 70:427–433

    Article  CAS  PubMed  Google Scholar 

  • Tokumoto M, Nagahama Y, Thomas P, Tokumoto T (2006) Cloning and identification of a membrane progestin receptor in goldfish ovaries and evidence it is an intermediary in oocyte meiotic maturation. Gen Comp Endocrinol 145:101–108

    Article  CAS  PubMed  Google Scholar 

  • Tubbs C, Thomas P (2009) Progestin signaling through an olfactory G protein and membrane progestin receptor-alpha in Atlantic croaker sperm: potential role in induction of sperm hypermotility. Endocrinology 150:473–484

    Article  CAS  PubMed  Google Scholar 

  • Wood PA, Bove K, You S, Chambers A, Hrushesky WJ (2005) Cancer growth and spread are saltatory and phase-locked to the reproductive cycle through mediators of angiogenesis. Mol Cancer Ther 4:1065–1075

    Article  CAS  PubMed  Google Scholar 

  • You S, Li W, Kobayashi M, Xiong Y, Hrushesky W, Wood P (2004) Creation of a stable mammary tumor cell line that maintains fertility-cycle tumor biology of the parent tumor. In Vitro Cell Dev Biol Anim 40:187–195

    Article  CAS  PubMed  Google Scholar 

  • Zhu Y, Bond J, Thomas P (2003a) Identification, classification, and partial characterization of genes in humans and other vertebrates homologous to a fish membrane progestin receptor. Proc Natl Acad Sci U S A 100:2237–2242

    Article  CAS  PubMed  Google Scholar 

  • Zhu Y, Rice CD, Pang Y, Pace M, Thomas P (2003b) Cloning, expression, and characterization of a membrane progestin receptor and evidence it is an intermediary in meiotic maturation of fish oocytes. Proc Natl Acad Sci U S A 100:2231–2236

    Article  CAS  PubMed  Google Scholar 

  • Zuo L, Li L, Wang Q, Fleming TP, You S (2009) Mammaglobin as a potential molecular target for breast cancer drug delivery. Cancer Cell Int 9:8

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Mr. Max Green (Atlanta Research & Educational Foundation, Atlanta VA Medical Center) for his assistance in editing the manuscript. This work is supported by Department of Defense Breast Cancer Research Program Synergy Idea Award and Atlanta Research and Education Foundation Bridge Fund (S. You).

Author information

Authors and Affiliations

  1. Histo—pathology core, Atlanta Research and Educational Foundation (151F), Atlanta VA Medical Center, 1670 Clairmont Road, Decatur, GA, 30033, USA

    Shaojin You & Lian Zuo

  2. Department of Pathology, Atlanta Research and Educational Foundation (151F), Atlanta VA Medical Center, 1670 Clairmont Road, Decatur, GA, 30033, USA

    Vijay Varma

Authors
  1. Shaojin You
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lian Zuo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vijay Varma
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shaojin You.

Rights and permissions

Reprints and permissions

About this article

Cite this article

You, S., Zuo, L. & Varma, V. Broad tissue expression of membrane progesterone receptor Alpha in normal mice. J Mol Hist 41, 101–110 (2010). https://doi.org/10.1007/s10735-010-9265-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10735-010-9265-7

Keywords

Search

Navigation