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Physiology of Progesterone

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Progestogens in Obstetrics and Gynecology

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Abstract

The major target organ of progesterone is the reproductive system. Progesterone, in association with estrogen, is involved in the development and sexual maturation of the reproductive organs and orchestrates the menstrual cycle. Progesterone takes part in all the processes from the preparation of the uterine decidua, myometrium and cervix during the menstrual cycle through blastocyst implantation and is the key hormone in pregnancy maintenance, sustaining of myometrial quiescence, cervical competence and modulation of the maternal immune system during pregnancy. Accumulating evidence suggests that, in humans, progesterone withdrawal during parturition is probably functional and involves a shift in the balance between progesterone and cortisol, as well as changes in the genomic and non-genomic effects of progesterone in the cellular level. This chapter describes the specific effects of progesterone on the uterus and the cervix during the normal menstrual cycle, and in maintenance of normal pregnancy, and during parturition. Progesterone also has numerous systemic effects and influences other organs outside the female reproductive tract.

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References

  1. Asdell SA. The growth and function of the corpus luteum. Physiol Rev. 1928;8:313–45.

    CAS  Google Scholar 

  2. Malpighi M. Opera omnia, seu thesaurus locupletissimus botanico-medico-anatomicus. Leiden: P. van der Aa; 1687

    Google Scholar 

  3. Fraenkel L. Die funktion des corpus luteum. Definition der theorie, ihre entstehung. Archiv Gynaekol. 1903;68:438–43.

    Google Scholar 

  4. Corner GW, Allen WM. Physiology of the corpus luteum, II: production of a special uterine reaction (progestational proliferation) by extracts of the corpus luteum. Am J Physiol. 1929;88:326–99.

    CAS  Google Scholar 

  5. Allen WM, Corner GW. Physiology of the corpus luteum, III: normal growth and implantation of embryos after very early ablation of the ovaries, and under the influence of extracts of the corpus luteum. Am J Physiol. 1929;88:340–6.

    CAS  Google Scholar 

  6. Allen WM. Physiology of the corpus luteum, V: the preparation and some chemical properties of progestin, a hormone of the corpus luteum which produces progestational proliferation. Am J Physiol. 1930;92:174–88.

    CAS  Google Scholar 

  7. Wintersteiner O, Allen WM. Crystalline progestin. J Biol Chem. 1934;107:321–36.

    CAS  Google Scholar 

  8. Slotta K, Ruschig H, Fels E. Reindarstellung der Hormone aus dem Corpus Luteum. Ber Dtsch Chem Ges. 1934;67:1270–3.

    Google Scholar 

  9. Hartmann M, Wettstein A. Ein krystallisiertes Hormon aus Corpus luteum. Helv Chim Acta. 1934;17:878–82.

    CAS  Google Scholar 

  10. Butenandt A, Westphal U. Zur Isolierung und Characterisierung des Corpus-luteum-Hormons. Ber Dtsch Chem Ges. 1934;67:1440–2.

    Google Scholar 

  11. Allen WM. Nomenclature of the corpus luteum hormone. Science. 1935;82:153.

    CAS  PubMed  Google Scholar 

  12. Graham JD, Clarke CL. Physiological action of progesterone in target tissues. Endocr Rev. 1997;18(4):502–19.

    CAS  PubMed  Google Scholar 

  13. Petersen SL, et al. Novel progesterone receptors: neural localization and possible functions. Front Neurosci. 2013;7:164.

    PubMed Central  PubMed  Google Scholar 

  14. Singh M, Su C, Ng S. Non-genomic mechanisms of progesterone action in the brain. Front Neurosci. 2013;7:159.

    PubMed Central  CAS  PubMed  Google Scholar 

  15. Nath A, Sitruk-Ware R. Different cardiovascular effects of progestins according to structure and activity. Climacteric. 2009;12 Suppl 1:96–101.

    CAS  PubMed  Google Scholar 

  16. Kaore SN, et al. Novel actions of progesterone: what we know today and what will be the scenario in the future? J Pharm Pharmacol. 2012;64(8):1040–62.

    CAS  PubMed  Google Scholar 

  17. DeMayo FJ, et al. Mechanisms of action of estrogen and progesterone. Ann N Y Acad Sci. 2002;955:48–59.

    CAS  PubMed  Google Scholar 

  18. Catt KJ. IV. Reproductive endocrinology. Lancet. 1970;1(7656):1097–104.

    CAS  PubMed  Google Scholar 

  19. An BS, et al. Differential role of progesterone receptor isoforms in the transcriptional regulation of human gonadotropin-releasing hormone I (GnRH I) receptor, GnRH I, and GnRH II.J Clin Endocrinol Metab. 2005;90(2):1106–13.

    CAS  PubMed  Google Scholar 

  20. Williams SP, Sigler PB. Atomic structure of progesterone complexed with its receptor. Nature. 1998;393(6683):392–6.

    CAS  PubMed  Google Scholar 

  21. Losel R, Wehling M. Nongenomic actions of steroid hormones. Nat Rev Mol Cell Biol. 2003;4(1):46–56.

    PubMed  Google Scholar 

  22. Losel RM, et al. Nongenomic steroid action: controversies, questions, and answers. Physiol Rev. 2003;83(3):965–1016.

    PubMed  Google Scholar 

  23. Tsai MJ, O’Malley BW. Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Annu Rev Biochem. 1994;63:451–86.

    CAS  PubMed  Google Scholar 

  24. Power RF, Conneely OM, O’Malley BW. New insights into activation of the steroid hormone receptor superfamily. Trends Pharmacol Sci. 1992;13(8):318–23.

    CAS  PubMed  Google Scholar 

  25. DeMarzo AM, et al. Dimerization of mammalian progesterone receptors occurs in the absence of DNA and is related to the release of the 90-kDa heat shock protein. Proc Natl Acad Sci U S A. 1991;88(1):72–6.

    PubMed Central  CAS  PubMed  Google Scholar 

  26. Brosens JJ, et al. Steroid receptor action. Best Pract Res Clin Obstet Gynaecol. 2004;18(2):265–83.

    PubMed  Google Scholar 

  27. Kastner P, et al. Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. EMBO J. 1990;9(5):1603–14.

    PubMed Central  CAS  PubMed  Google Scholar 

  28. Meyer ME, et al. A limiting factor mediates the differential activation of promoters by the human progesterone receptor isoforms. J Biol Chem. 1992;267(15):10882–7.

    CAS  PubMed  Google Scholar 

  29. Vegeto E, et al. Human progesterone receptor A form is a cell- and promoter-specific repressor of human progesterone receptor B function. Mol Endocrinol. 1993;7(10):1244–55.

    CAS  PubMed  Google Scholar 

  30. Hirata S, et al. Isoform/variant mRNAs for sex steroid hormone receptors in humans. Trends Endocrinol Metab. 2003;14(3):124–9.

    CAS  PubMed  Google Scholar 

  31. Sartorius CA, et al. A third transactivation function (AF3) of human progesterone receptors located in the unique N-terminal segment of the B-isoform. Mol Endocrinol. 1994;8(10):1347–60.

    CAS  PubMed  Google Scholar 

  32. Huse B, et al. Definition of a negative modulation domain in the human progesterone receptor. Mol Endocrinol. 1998;12(9):1334–42.

    CAS  PubMed  Google Scholar 

  33. Wildman DE, et al. Evolutionary history of the progesterone receptor in primates. J Soc Gynecol Investig. 2006;13(2):238A.

    Google Scholar 

  34. Wei LL, et al. 5′-Heterogeneity in human progesterone receptor transcripts predicts a new amino-terminal truncated “C”-receptor and unique A-receptor messages. Mol Endocrinol. 1990;4(12):1833–40.

    CAS  PubMed  Google Scholar 

  35. Wei LL, et al. An amino-terminal truncated progesterone receptor isoform, PRc, enhances progestin-induced transcriptional activity. Mol Endocrinol. 1996;10(11):1379–87.

    CAS  PubMed  Google Scholar 

  36. Condon JC, et al. Up-regulation of the progesterone receptor (PR)-C isoform in laboring myometrium by activation of nuclear factor-kappaB may contribute to the onset of labor through inhibition of PR function. Mol Endocrinol. 2006;20(4):764–75.

    CAS  PubMed  Google Scholar 

  37. Wei LL, Norris BM, Baker CJ. An N-terminally truncated third progesterone receptor protein, PR(C), forms heterodimers with PR(B) but interferes in PR(B)-DNA binding. J Steroid Biochem Mol Biol. 1997;62(4):287–97.

    CAS  PubMed  Google Scholar 

  38. Hirata S, et al. The novel isoform of the estrogen receptor-alpha cDNA (ERalpha isoform S cDNA) in the human testis. J Steroid Biochem Mol Biol. 2002;80(3):299–305.

    CAS  PubMed  Google Scholar 

  39. Saner KJ, et al. Cloning and expression of a novel, truncated, progesterone receptor. Mol Cell Endocrinol. 2003;200(1–2):155–63.

    CAS  PubMed  Google Scholar 

  40. Samalecos A, Gellersen B. Systematic expression analysis and antibody screening do not support the existence of naturally occurring progesterone receptor (PR)-C, PR-M, or other truncated PR isoforms. Endocrinology. 2008;149(11):5872–87.

    CAS  PubMed  Google Scholar 

  41. Madsen G, et al. Progesterone receptor or cytoskeletal protein? Reprod Sci. 2007;14(3):217–22.

    CAS  PubMed  Google Scholar 

  42. Kumar R, et al. The clinical relevance of steroid hormone receptor corepressors. Clin Cancer Res. 2005;11(8):2822–31.

    CAS  PubMed  Google Scholar 

  43. Lee K, et al. Molecular mechanisms involved in progesterone receptor regulation of uterine function. J Steroid Biochem Mol Biol. 2006;102(1–5):41–50.

    PubMed Central  CAS  PubMed  Google Scholar 

  44. Spelsberg TC, Steggles AW, O’Malley BW. Progesterone-binding components of chick oviduct. 3. Chromatin acceptor sites. J Biol Chem. 1971;246(13):4188–97.

    CAS  PubMed  Google Scholar 

  45. Gao X, Loggie BW, Nawaz Z. The roles of sex steroid receptor coregulators in cancer. Mol Cancer. 2002;1:7.

    PubMed Central  PubMed  Google Scholar 

  46. Mukherjee A, et al. Steroid receptor coactivator 2 is essential for progesterone-dependent uterine function and mammary morphogenesis: insights from the mouse–implications for the human. J Steroid Biochem Mol Biol. 2006;102(1–5):22–31.

    CAS  PubMed  Google Scholar 

  47. Fernandez-Valdivia R, et al. Progesterone-action in the murine uterus and mammary gland requires steroid receptor coactivator 2: relevance to the human. Front Biosci. 2007;12:3640–7.

    CAS  PubMed  Google Scholar 

  48. McKenna NJ, O’Malley BW. Combinatorial control of gene expression by nuclear receptors and coregulators. Cell. 2002;108(4):465–74.

    CAS  PubMed  Google Scholar 

  49. Smith CL, O’Malley BW. Coregulator function: a key to understanding tissue specificity of selective receptor modulators. Endocr Rev. 2004;25(1):45–71.

    CAS  PubMed  Google Scholar 

  50. Xu J, et al. Partial hormone resistance in mice with disruption of the steroid receptor coactivator-1 (SRC-1) gene. Science. 1998;279(5358):1922–5.

    CAS  PubMed  Google Scholar 

  51. Han SJ, et al. Steroid receptor coactivator (SRC)-1 and SRC-3 differentially modulate tissue-specific activation functions of the progesterone receptor. Mol Endocrinol. 2006;20(1):45–55.

    CAS  PubMed  Google Scholar 

  52. Xu J, et al. The steroid receptor coactivator SRC-3 (p/CIP/RAC3/AIB1/ACTR/TRAM-1) is required for normal growth, puberty, female reproductive function, and mammary gland development. Proc Natl Acad Sci U S A. 2000;97(12):6379–84.

    PubMed Central  CAS  PubMed  Google Scholar 

  53. Heery DM, et al. A signature motif in transcriptional co-activators mediates binding to nuclear receptors. Nature. 1997;387(6634):733–6.

    CAS  PubMed  Google Scholar 

  54. Aoyagi S, Archer TK. Dynamic histone acetylation/deacetylation with progesterone receptor-mediated transcription. Mol Endocrinol. 2007;21(4):843–56.

    CAS  PubMed  Google Scholar 

  55. Blackmore PF, Lattanzio FA. Cell surface localization of a novel non-genomic progesterone receptor on the head of human sperm. Biochem Biophys Res Commun. 1991;181(1):331–6.

    CAS  PubMed  Google Scholar 

  56. Baldi E, et al. Intracellular calcium accumulation and responsiveness to progesterone in capacitating human spermatozoa. J Androl. 1991;12(5):323–30.

    CAS  PubMed  Google Scholar 

  57. Luconi M, et al. Identification and characterization of functional nongenomic progesterone receptors on human sperm membrane. J Clin Endocrinol Metab. 1998;83(3):877–85.

    CAS  PubMed  Google Scholar 

  58. Falkenstein E, et al. Specific progesterone binding to a membrane protein and related nongenomic effects on Ca2 + -fluxes in sperm. Endocrinology. 1999;140(12):5999–6002.

    CAS  PubMed  Google Scholar 

  59. Patrat C, Serres C, Jouannet P. Induction of a sodium ion influx by progesterone in human spermatozoa. Biol Reprod. 2000;62(5):1380–6.

    CAS  PubMed  Google Scholar 

  60. Turner KO, Meizel S. Progesterone-mediated efflux of cytosolic chloride during the human sperm acrosome reaction. Biochem Biophys Res Commun. 1995;213(3):774–80.

    CAS  PubMed  Google Scholar 

  61. Finidori-Lepicard J, et al. Progesterone inhibits membrane-bound adenylate cyclase in Xenopus laevis oocytes. Nature. 1981;292(5820):255–7.

    CAS  PubMed  Google Scholar 

  62. Grosse B, et al. Membrane signalling and progesterone in female and male osteoblasts. I. Involvement of intracellular Ca(2+), inositol trisphosphate, and diacylglycerol, but not cAMP. J Cell Biochem. 2000;79(2):334–45.

    CAS  PubMed  Google Scholar 

  63. Le Mellay V, Lieberherr M. Membrane signaling and progesterone in female and male osteoblasts. II. Direct involvement of G alpha q/11 coupled to PLC-beta 1 and PLC-beta 3. J Cell Biochem. 2000;79(2):173–81.

    CAS  PubMed  Google Scholar 

  64. Maller JL, Krebs EG. Progesterone-stimulated meiotic cell division in Xenopus oocytes. Induction by regulatory subunit and inhibition by catalytic subunit of adenosine 3′:5′-monophosphate-dependent protein kinase. J Biol Chem. 1977;252(5):1712–8.

    CAS  PubMed  Google Scholar 

  65. Ishikawa K, et al. Primary action of steroid hormone at the surface of amphibian oocyte in the induction of germinal vesicle breakdown. Mol Cell Endocrinol. 1977;9(1):91–100.

    CAS  PubMed  Google Scholar 

  66. Baulieu EE, et al. Steroid-induced meiotic division in Xenopus laevis oocytes: surface and calcium. Nature. 1978;275(5681):593–8.

    CAS  PubMed  Google Scholar 

  67. Meizel S, Turner KO. Progesterone acts at the plasma membrane of human sperm. Mol Cell Endocrinol. 1991;77(1–3):R1–5.

    CAS  PubMed  Google Scholar 

  68. Meyer C, et al. Purification and partial sequencing of high-affinity progesterone-binding site(s) from porcine liver membranes. Eur J Biochem. 1996;239(3):726–31.

    CAS  PubMed  Google Scholar 

  69. Falkenstein E, et al. Full-length cDNA sequence of a progesterone membrane-binding protein from porcine vascular smooth muscle cells. Biochem Biophys Res Commun. 1996;229(1):86–9.

    CAS  PubMed  Google Scholar 

  70. Krebs CJ, et al. A membrane-associated progesterone-binding protein, 25-Dx, is regulated by progesterone in brain regions involved in female reproductive behaviors. Proc Natl Acad Sci U S A. 2000;97(23):12816–21.

    PubMed Central  CAS  PubMed  Google Scholar 

  71. Zhu Y, Bond J, Thomas P. 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. 2003;100(5):2237–42.

    PubMed Central  CAS  PubMed  Google Scholar 

  72. White HD, et al. Mucosal immunity in the human female reproductive tract: cytotoxic T lymphocyte function in the cervix and vagina of premenopausal and postmenopausal women. Am J Reprod Immunol. 1997;37(1):30–8.

    CAS  PubMed  Google Scholar 

  73. Wira C, et al. Effect of the menstrual cycle on immunological parameters in the human female reproductive tract. J Acquir Immune Defic Syndr. 2005;38 Suppl 1:S34–6.

    PubMed  Google Scholar 

  74. Wira CR, Rossoll RM. Antigen-presenting cells in the female reproductive tract: influence of sex hormones on antigen presentation in the vagina. Immunology. 1995;84(4):505–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  75. Walch KT, Huber JC. Progesterone for recurrent miscarriage: truth and deceptions. Best Pract Res Clin Obstet Gynaecol. 2008;22(2):375–89.

    PubMed  Google Scholar 

  76. De M, Wood GW. Influence of oestrogen and progesterone on macrophage distribution in the mouse uterus. J Endocrinol. 1990;126(3):417–24.

    CAS  PubMed  Google Scholar 

  77. Hanna J, et al. Decidual NK cells regulate key developmental processes at the human fetal-maternal interface. Nat Med. 2006;12(9):1065–74.

    CAS  PubMed  Google Scholar 

  78. Croy BA, et al. Decidual natural killer cells: key regulators of placental development (a review). J Reprod Immunol. 2002;57(1–2):151–68.

    CAS  PubMed  Google Scholar 

  79. Beagley KW, Gockel CM. Regulation of innate and adaptive immunity by the female sex hormones oestradiol and progesterone. FEMS Immunol Med Microbiol. 2003;38(1):13–22.

    CAS  PubMed  Google Scholar 

  80. Henderson TA, et al. Steroid receptor expression in uterine natural killer cells. J Clin Endocrinol Metab. 2003;88(1):440–9.

    CAS  PubMed  Google Scholar 

  81. Verma S, et al. Human decidual natural killer cells express the receptor for and respond to the cytokine interleukin 15. Biol Reprod. 2000;62(4):959–68.

    CAS  PubMed  Google Scholar 

  82. Roussev RG, Higgins NG, McIntyre JA. Phenotypic characterization of normal human placental mononuclear cells. J Reprod Immunol. 1993;25(1):15–29.

    CAS  PubMed  Google Scholar 

  83. Chao KH, et al. Decidual natural killer cytotoxicity decreased in normal pregnancy but not in anembryonic pregnancy and recurrent spontaneous abortion. Am J Reprod Immunol. 1995;34(5):274–80.

    CAS  PubMed  Google Scholar 

  84. Piccinni MP, Maggi E, Romagnani S. Role of hormone-controlled T-cell cytokines in the maintenance of pregnancy. Biochem Soc Trans. 2000;28(2):212–5.

    CAS  PubMed  Google Scholar 

  85. Szekeres-Bartho J, Wegmann TG. A progesterone-dependent immunomodulatory protein alters the Th1/Th2 balance. J Reprod Immunol. 1996;31(1–2):81–95.

    CAS  PubMed  Google Scholar 

  86. Saito S. Cytokine network at the feto-maternal interface. J Reprod Immunol. 2000;47(2):87–103.

    CAS  PubMed  Google Scholar 

  87. Eblen AC, et al. Alterations in humoral immune responses associated with recurrent pregnancy loss. Fertil Steril. 2000;73(2):305–13.

    CAS  PubMed  Google Scholar 

  88. Druckmann R, Druckmann MA. Progesterone and the immunology of pregnancy. J Steroid Biochem Mol Biol. 2005;97(5):389–96.

    CAS  PubMed  Google Scholar 

  89. Szekeres-Bartho J, et al. The mechanism of the inhibitory effect of progesterone on lymphocyte cytotoxicity: I. Progesterone-treated lymphocytes release a substance inhibiting cytotoxicity and prostaglandin synthesis. Am J Reprod Immunol Microbiol. 1985;9(1):15–8.

    CAS  PubMed  Google Scholar 

  90. Kelemen K, et al. A progesterone-induced protein increases the synthesis of asymmetric antibodies. Cell Immunol. 1996;167(1):129–34.

    CAS  PubMed  Google Scholar 

  91. Faust Z, et al. Progesterone-induced blocking factor inhibits degranulation of natural killer cells. Am J Reprod Immunol. 1999;42(2):71–5.

    CAS  PubMed  Google Scholar 

  92. Laskarin G, et al. Progesterone induced blocking factor (PIBF) mediates progesterone induced suppression of decidual lymphocyte cytotoxicity. Am J Reprod Immunol. 2002;48(4):201–9.

    PubMed  Google Scholar 

  93. Jabbour HN, et al. Endocrine regulation of menstruation. Endocr Rev. 2006;27(1):17–46.

    CAS  PubMed  Google Scholar 

  94. Gambino LS, et al. Angiogenesis occurs by vessel elongation in proliferative phase human endometrium. Hum Reprod. 2002;17(5):1199–206.

    PubMed  Google Scholar 

  95. Noyes RW, Hertig AT, Rock J. Dating the endometrial biopsy. Am J Obstet Gynecol. 1975;122(2):262–3.

    CAS  PubMed  Google Scholar 

  96. Lerner LJ. Hormone antagonists: inhibitors of specific activities of estrogen and androgen. Recent Prog Horm Res. 1964;20:435–90.

    CAS  PubMed  Google Scholar 

  97. Hsueh AJ, Peck Jr EJ, Clark JH. Progesterone antagonism of the oestrogen receptor and oestrogen-induced uterine growth. Nature. 1975;254(5498):337–9.

    CAS  PubMed  Google Scholar 

  98. Tseng L, Gurpide E. Induction of human endometrial estradiol dehydrogenase by progestins. Endocrinology. 1975;97(4):825–33.

    CAS  PubMed  Google Scholar 

  99. Kirkland JL, Murthy L, Stancel GM. Progesterone inhibits the estrogen-induced expression of c-fos messenger ribonucleic acid in the uterus. Endocrinology. 1992;130(6):3223–30.

    CAS  PubMed  Google Scholar 

  100. Lockwood CJ, et al. The role of progestationally regulated stromal cell tissue factor and type-1 plasminogen activator inhibitor (PAI-1) in endometrial hemostasis and menstruation. Ann N Y Acad Sci. 1994;734:57–79.

    CAS  PubMed  Google Scholar 

  101. Lockwood CJ, et al. Biological mechanisms underlying RU 486 clinical effects: inhibition of endometrial stromal cell tissue factor content. J Clin Endocrinol Metab. 1994;79(3):786–90.

    CAS  PubMed  Google Scholar 

  102. Cibils LA. Contractility of the nonpregnant human uterus. Obstet Gynecol. 1967;30(3):441–61.

    CAS  PubMed  Google Scholar 

  103. Bulletti C, et al. Uterine contractility during the menstrual cycle. Hum Reprod. 2000;15 Suppl 1:81–9.

    PubMed  Google Scholar 

  104. de Ziegler D, et al. Contractility of the nonpregnant uterus: the follicular phase. Ann N Y Acad Sci. 2001;943:172–84.

    PubMed  Google Scholar 

  105. Noe M, et al. The cyclic pattern of the immunocytochemical expression of oestrogen and progesterone receptors in human myometrial and endometrial layers: characterization of the endometrial-subendometrial unit. Hum Reprod. 1999;14(1):190–7.

    CAS  PubMed  Google Scholar 

  106. Akerlund M, Batra S, Helm G. Comparison of plasma and myometrial tissue concentrations of estradiol-17 beta and progesterone in nonpregnant women. Contraception. 1981;23(4):447–55.

    CAS  PubMed  Google Scholar 

  107. Batra S, Sjoberg NO, Thorbert G. Sex steroids in plasma and reproductive tissues of the female guinea pig. Biol Reprod. 1980;22(3):430–7.

    CAS  PubMed  Google Scholar 

  108. Jordan J, Albert S. The Cervix. 2nd ed. Oxford, United Kingdom: Blackwell Publising; 2007.

    Google Scholar 

  109. Cano A, et al. Expression of estrogen receptors, progesterone receptors, and an estrogen receptor-associated protein in the human cervix during the menstrual cycle and menopause. Fertil Steril. 1990;54(6):1058–64.

    CAS  PubMed  Google Scholar 

  110. Gorodeski GI. Effects of menopause and estrogen on cervical epithelial permeability. J Clin Endocrinol Metab. 2000;85(7):2584–95.

    CAS  PubMed  Google Scholar 

  111. Odeblad E. Physical properties of cervical mucus. Adv Exp Med Biol. 1977;89:217–25.

    CAS  PubMed  Google Scholar 

  112. Snijders MP, et al. Immunocytochemical analysis of oestrogen receptors and progesterone receptors in the human uterus throughout the menstrual cycle and after the menopause. J Reprod Fertil. 1992;94(2):363–71.

    CAS  PubMed  Google Scholar 

  113. Odeblad E. The physics of the cervical mucus. Acta Obstet Gynecol Scand Suppl. 1959;38(Supp 1):44–58.

    CAS  PubMed  Google Scholar 

  114. Odeblad E. Undulations of macromolecules in cervical mucus. Int J Fertil. 1962;7:313–9.

    CAS  PubMed  Google Scholar 

  115. Odeblad E, WESTIN B. Studies on the penetration of radioactive ions through human cervical mucus. Acta Radiol. 1958;49(5):382–8.

    CAS  PubMed  Google Scholar 

  116. Croxatto HB. Mechanisms that explain the contraceptive action of progestin implants for women. Contraception. 2002;65(1):21–7.

    CAS  PubMed  Google Scholar 

  117. Erkkola R, Landgren BM. Role of progestins in contraception. Acta Obstet Gynecol Scand. 2005;84(3):207–16.

    PubMed  Google Scholar 

  118. Mesiano S. Roles of estrogen and progesterone in human parturition. Front Horm Res. 2001;27:86–104.

    CAS  PubMed  Google Scholar 

  119. Tulchinsky D, Hobel CJ. Plasma human chorionic gonadotropin, estrone, estradiol, estriol, progesterone, and 17 alpha-hydroxyprogesterone in human pregnancy. 3. Early normal pregnancy. Am J Obstet Gynecol. 1973;117(7):884–93.

    CAS  PubMed  Google Scholar 

  120. Johansson ED. Plasma levels of progesterone in pregnancy measured by a rapid competitive protein binding technique. Acta Endocrinol (Copenh). 1969;61(4):607–17.

    CAS  Google Scholar 

  121. Csapo AI, Pulkkinen MO, Wiest WG. Effects of luteectomy and progesterone replacement therapy in early pregnant patients. Am J Obstet Gynecol. 1973;115(6):759–65.

    CAS  PubMed  Google Scholar 

  122. Tulchinsky D, Okada D. Hormones in human pregnancy. IV Plasma progesterone. Am J Obstet Gynecol. 1975;121(3):293–9.

    CAS  PubMed  Google Scholar 

  123. Sippell WG, et al. Concentrations of aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol, and cortisone determined simultaneously in human amniotic fluid throughout gestation. J Clin Endocrinol Metab. 1981;52(3):385–92.

    CAS  PubMed  Google Scholar 

  124. Nagamani M, et al. Maternal and amniotic fluid steroids throughout human pregnancy. Am J Obstet Gynecol. 1979;134(6):674–80.

    CAS  PubMed  Google Scholar 

  125. Ohana E, et al. Maternal plasma and amniotic fluid cortisol and progesterone concentrations between women with and without term labor. A comparison. J Reprod Med. 1996;41(2):80–6.

    CAS  PubMed  Google Scholar 

  126. Mazor M, et al. Maternal plasma and amniotic fluid 17 beta-estradiol, progesterone and cortisol concentrations in women with successfully and unsuccessfully treated preterm labor. Arch Gynecol Obstet. 1996;258(2):89–96.

    CAS  PubMed  Google Scholar 

  127. Gorodeski IG, et al. Progesterone (P) receptor dynamics in estrogen primed normal human cervix following P injection. Fertil Steril. 1987;47(1):108–13.

    CAS  PubMed  Google Scholar 

  128. Chwalisz K. The use of progesterone antagonists for cervical ripening and as an adjunct to labour and delivery. Hum Reprod. 1994;9 Suppl 1:131–61.

    CAS  PubMed  Google Scholar 

  129. Stjernholm Y, et al. Cervical ripening in humans: potential roles of estrogen, progesterone, and insulin-like growth factor-I. Am J Obstet Gynecol. 1996;174(3):1065–71.

    CAS  PubMed  Google Scholar 

  130. Bernal AL. Overview of current research in parturition. Exp Physiol. 2001;86(2):213–22.

    CAS  PubMed  Google Scholar 

  131. Karim SM, Hillier K. Prostaglandins in the control of animal and human reproduction. Br Med Bull. 1979;35(2):173–80.

    CAS  PubMed  Google Scholar 

  132. Zakar T, Hertelendy F. Progesterone withdrawal: key to parturition. Am J Obstet Gynecol. 2007;196(4):289–96.

    CAS  PubMed  Google Scholar 

  133. Thorburn GD, Challis J, Currie WB. Control of parturition in domestic animals. Biol Reprod. 1977;16(1):18–27.

    CAS  PubMed  Google Scholar 

  134. Mendelson CR, Condon JC. New insights into the molecular endocrinology of parturition. J Steroid Biochem Mol Biol. 2005;93(2–5):113–9.

    CAS  PubMed  Google Scholar 

  135. Mahendroo MS, et al. The parturition defect in steroid 5alpha-reductase type 1 knockout mice is due to impaired cervical ripening. Mol Endocrinol. 1999;13(6):981–92.

    CAS  PubMed  Google Scholar 

  136. Bygdeman M, et al. The use of progesterone antagonists in combination with prostaglandin for termination of pregnancy. Hum Reprod. 1994;9 Suppl 1:121–5.

    PubMed  Google Scholar 

  137. Puri CP, et al. Effects of progesterone antagonist ZK 98.299 on early pregnancy and foetal outcome in bonnet monkeys. Contraception. 1990;41(2):197–205.

    CAS  PubMed  Google Scholar 

  138. Westphal U, Stroupe SD, Cheng SL. Progesterone binding to serum proteins. Ann N Y Acad Sci. 1977;286:10–28.

    CAS  PubMed  Google Scholar 

  139. Karalis K, Goodwin G, Majzoub JA. Cortisol blockade of progesterone: a possible molecular mechanism involved in the initiation of human labor. Nat Med. 1996;2(5):556–60.

    CAS  PubMed  Google Scholar 

  140. Milewich L, et al. Initiation of human parturition. VIII. Metabolism of progesterone by fetal membranes of early and late human gestation. Obstet Gynecol. 1977;50(1):45–8.

    CAS  PubMed  Google Scholar 

  141. Mitchell BF, Wong S. Changes in 17 beta,20 alpha-hydroxysteroid dehydrogenase activity supporting an increase in the estrogen/progesterone ratio of human fetal membranes at parturition. Am J Obstet Gynecol. 1993;168(5):1377–85.

    CAS  PubMed  Google Scholar 

  142. Pieber D, et al. Interactions between progesterone receptor isoforms in myometrial cells in human labour. Mol Hum Reprod. 2001;7(9):875–9.

    CAS  PubMed  Google Scholar 

  143. Rezapour M, et al. Sex steroid receptors and human parturition. Obstet Gynecol. 1997;89(6):918–24.

    CAS  PubMed  Google Scholar 

  144. How H, et al. Myometrial estradiol and progesterone receptor changes in preterm and term pregnancies. Obstet Gynecol. 1995;86(6):936–40.

    CAS  PubMed  Google Scholar 

  145. Tan H, et al. Progesterone receptor-A and -B have opposite effects on proinflammatory gene expression in human myometrial cells: implications for progesterone actions in human pregnancy and parturition. J Clin Endocrinol Metab. 2012;97(5):E719–30.

    PubMed Central  CAS  PubMed  Google Scholar 

  146. Challis JRG, et al. Endocrine and paracrine regulation of birth at term and preterm. Endocr Rev. 2000;21(5):514–50.

    CAS  PubMed  Google Scholar 

  147. Fu X, et al. Unexpected stimulatory effect of progesterone on human myometrial contractile activity in vitro. Obstet Gynecol. 1993;82(1):23–8.

    CAS  PubMed  Google Scholar 

  148. Fu X, et al. Antitachyphylactic effects of progesterone and oxytocin on term human myometrial contractile activity in vitro. Obstet Gynecol. 1993;82(4 Pt 1):532–8.

    CAS  PubMed  Google Scholar 

  149. Mesiano S. Myometrial progesterone responsiveness. Semin Reprod Med. 2007;25(1):5–13.

    CAS  PubMed  Google Scholar 

  150. Merlino AA, et al. Nuclear progesterone receptors in the human pregnancy myometrium: evidence that parturition involves functional progesterone withdrawal mediated by increased expression of progesterone receptor-A. J Clin Endocrinol Metab. 2007;92(5):1927–33.

    CAS  PubMed  Google Scholar 

  151. Pieber D, Allport VC, Bennett PR. Progesterone receptor isoform A inhibits isoform B-mediated transactivation in human amnion. Eur J Pharmacol. 2001;427(1):7–11.

    CAS  PubMed  Google Scholar 

  152. Mesiano S, et al. Progesterone withdrawal and estrogen activation in human parturition are coordinated by progesterone receptor A expression in the myometrium. J Clin Endocrinol Metab. 2002;87(6):2924–30.

    CAS  PubMed  Google Scholar 

  153. Haluska GJ, et al. Progesterone receptor localization and isoforms in myometrium, decidua, and fetal membranes from rhesus macaques: evidence for functional progesterone withdrawal at parturition. J Soc Gynecol Investig. 2002;9(3):125–36.

    CAS  PubMed  Google Scholar 

  154. Madsen G, et al. Prostaglandins differentially modulate progesterone receptor-A and -B expression in human myometrial cells: evidence for prostaglandin-induced functional progesterone withdrawal. J Clin Endocrinol Metab. 2004;89(2):1010–3.

    CAS  PubMed  Google Scholar 

  155. Karteris E, et al. Progesterone signaling in human myometrium through two novel membrane G protein-coupled receptors: potential role in functional progesterone withdrawal at term. Mol Endocrinol. 2006;20(7):1519–34.

    CAS  PubMed  Google Scholar 

  156. Haukkamaa M. High affinity progesterone binding sites of human uterine microsomal membranes. J Steroid Biochem. 1984;20(2):569–73.

    CAS  PubMed  Google Scholar 

  157. Fernandes MS, et al. Regulated expression of putative membrane progestin receptor homologues in human endometrium and gestational tissues. J Endocrinol. 2005;187(1):89–101.

    CAS  PubMed  Google Scholar 

  158. Nissenson R, Fluoret G, Hechter O. Opposing effects of estradiol and progesterone on oxytocin receptors in rabbit uterus. Proc Natl Acad Sci U S A. 1978;75(4):2044–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  159. Soloff MS, et al. Regulation of oxytocin receptor concentration in rat uterine explants by estrogen and progesterone. Can J Biochem Cell Biol. 1983;61(7):625–30.

    CAS  PubMed  Google Scholar 

  160. Larcher A, et al. Oxytocin receptor gene expression in the rat uterus during pregnancy and the estrous cycle and in response to gonadal steroid treatment. Endocrinology. 1995;136(12):5350–6.

    CAS  PubMed  Google Scholar 

  161. KNAUS H. Zur Physiologie des Corpus luteum. Arch Gynak. 1929;138(1):201–16.

    Google Scholar 

  162. Grazzini E, et al. Inhibition of oxytocin receptor function by direct binding of progesterone. Nature. 1998;392(6675):509–12.

    CAS  PubMed  Google Scholar 

  163. Astle S, Khan RN, Thornton S. The effects of a progesterone metabolite, 5 beta-dihydroprogesterone, on oxytocin receptor binding in human myometrial membranes. BJOG. 2003;110(6):589–92.

    CAS  PubMed  Google Scholar 

  164. Gimpl G, Fahrenholz F. The oxytocin receptor system: structure, function, and regulation. Physiol Rev. 2001;81(2):629–83.

    CAS  PubMed  Google Scholar 

  165. Gimpl G, et al. Oxytocin receptors and cholesterol: interaction and regulation. Exp Physiol 2000;85 Spec No:41S–49S

    Google Scholar 

  166. Debry P, et al. Role of multidrug resistance P-glycoproteins in cholesterol esterification. J Biol Chem. 1997;272(2):1026–31.

    CAS  PubMed  Google Scholar 

  167. Smart EJ, et al. A role for caveolin in transport of cholesterol from endoplasmic reticulum to plasma membrane. J Biol Chem. 1996;271(46):29427–35.

    CAS  PubMed  Google Scholar 

  168. Metherall JE, Waugh K, Li H. Progesterone inhibits cholesterol biosynthesis in cultured cells. Accumulation of cholesterol precursors. J Biol Chem. 1996;271(5):2627–33.

    CAS  PubMed  Google Scholar 

  169. Gimpl G, Fahrenholz F. Human oxytocin receptors in cholesterol-rich vs. cholesterol-poor microdomains of the plasma membrane. Eur J Biochem. 2000;267(9):2483–97.

    CAS  PubMed  Google Scholar 

  170. Klein U, Gimpl G, Fahrenholz F. Alteration of the myometrial plasma membrane cholesterol content with beta-cyclodextrin modulates the binding affinity of the oxytocin receptor. Biochemistry. 1995;34(42):13784–93.

    CAS  PubMed  Google Scholar 

  171. Kofinas AD, et al. Progesterone and estradiol concentrations in nonpregnant and pregnant human myometrium. Effect of progesterone and estradiol on cyclic adenosine monophosphate-phosphodiesterase activity. J Reprod Med. 1990;35(11):1045–50.

    CAS  PubMed  Google Scholar 

  172. Fomin VP, Cox BE, Word RA. Effect of progesterone on intracellular Ca2+ homeostasis in human myometrial smooth muscle cells. Am J Physiol. 1999;276(2 Pt 1):C379–85.

    CAS  PubMed  Google Scholar 

  173. Lindstrom TM, Bennett PR. The role of nuclear factor kappa B in human labour. Reproduction. 2005;130(5):569–81.

    CAS  PubMed  Google Scholar 

  174. Lappas M, Rice GE. The role and regulation of the nuclear factor kappa B signalling pathway in human labour. Placenta. 2007;28(5–6):543–56.

    CAS  PubMed  Google Scholar 

  175. Condon JC, et al. Surfactant protein secreted by the maturing mouse fetal lung acts as a hormone that signals the initiation of parturition. Proc Natl Acad Sci U S A. 2004;101(14):4978–83.

    PubMed Central  CAS  PubMed  Google Scholar 

  176. Lappas M, Permezel M, Rice GE. Advanced glycation end products mediate pro-inflammatory actions in human gestational tissues via nuclear factor-kappaB and extracellular signal-regulated kinase 1/2. J Endocrinol. 2007;193(2):269–77.

    CAS  PubMed  Google Scholar 

  177. Mohan AR, et al. The effect of mechanical stretch on cyclooxygenase type 2 expression and activator protein-1 and nuclear factor-kappaB activity in human amnion cells. Endocrinology. 2007;148(4):1850–7.

    CAS  PubMed  Google Scholar 

  178. Karalis K, et al. Autocrine or paracrine inflammatory actions of corticotropin-releasing hormone in vivo. Science. 1991;254(5030):421–3.

    CAS  PubMed  Google Scholar 

  179. Kalkhoven E, et al. Negative interaction between the RelA(p65) subunit of NF-kappaB and the progesterone receptor. J Biol Chem. 1996;271(11):6217–24.

    CAS  PubMed  Google Scholar 

  180. Allport VC, et al. Human labour is associated with nuclear factor-kappaB activity which mediates cyclo-oxygenase-2 expression and is involved with the ‘functional progesterone withdrawal’. Mol Hum Reprod. 2001;7(6):581–6.

    CAS  PubMed  Google Scholar 

  181. Hardy DB, et al. Progesterone receptor plays a major antiinflammatory role in human myometrial cells by antagonism of nuclear factor-kappaB activation of cyclooxygenase 2 expression. Mol Endocrinol. 2006;20(11):2724–33.

    CAS  PubMed  Google Scholar 

  182. Srivastava MD, Anderson DJ. Progesterone receptor expression by human leukocyte cell lines: molecular mechanisms of cytokine suppression. Clin Exp Obstet Gynecol. 2007;34(1):14–24.

    CAS  PubMed  Google Scholar 

  183. Ito A, et al. Suppression of interleukin 8 production by progesterone in rabbit uterine cervix. Biochem J. 1994;301(Pt 1):183–6.

    PubMed Central  CAS  PubMed  Google Scholar 

  184. Vidaeff AC, et al. Impact of progesterone on cytokine-stimulated nuclear factor-kappaB signaling in HeLa cells. J Matern Fetal Neonatal Med. 2007;20(1):23–8.

    CAS  PubMed  Google Scholar 

  185. Condon JC, et al. A decline in the levels of progesterone receptor coactivators in the pregnant uterus at term may antagonize progesterone receptor function and contribute to the initiation of parturition. Proc Natl Acad Sci U S A. 2003;100(16):9518–23.

    PubMed Central  CAS  PubMed  Google Scholar 

  186. Dong X, et al. Identification and characterization of the protein-associated splicing factor as a negative co-regulator of the progesterone receptor. J Biol Chem. 2005;280(14):13329–40.

    CAS  PubMed  Google Scholar 

  187. Tyson-Capper AJ, Shiells EA, Robson SC. Interplay between polypyrimidine tract binding protein-associated splicing factor and human myometrial progesterone receptors. J Mol Endocrinol. 2009;43(1):29–41.

    CAS  PubMed  Google Scholar 

  188. Xie N, et al. Expression and function of myometrial PSF suggest a role in progesterone withdrawal and the initiation of labor. Mol Endocrinol. 2012;26(8):1370–9.

    CAS  PubMed  Google Scholar 

  189. Goldman S, et al. Progesterone receptor expression in human decidua and fetal membranes before and after contractions: possible mechanism for functional progesterone withdrawal. Mol Hum Reprod. 2005;11(4):269–77.

    CAS  PubMed  Google Scholar 

  190. Oh SY, et al. Progesterone receptor isoform (A/B) ratio of human fetal membranes increases during term parturition. Am J Obstet Gynecol. 2005;193(3 Pt 2):1156–60.

    CAS  PubMed  Google Scholar 

  191. Mills AA, et al. Characterization of progesterone receptor isoform expression in fetal membranes. Am J Obstet Gynecol. 2006;195(4):998–1003.

    CAS  PubMed  Google Scholar 

  192. Taylor AH, et al. The progesterone receptor in human term amniochorion and placenta is isoform C. Endocrinology. 2006;147(2):687–93.

    CAS  PubMed  Google Scholar 

  193. Taylor AH, et al. The cytoplasmic 60 kDa progesterone receptor isoform predominates in the human amniochorion and placenta at term. Reprod Biol Endocrinol. 2009;7:22.

    PubMed Central  PubMed  Google Scholar 

  194. Uldbjerg N, Ekman G, Malmstrom A. Ripening of the human uterine cervix related to changes in collagen, glycosaminoglycans and collagenolytic activity. Am J Obstet Gynecol. 1982;147:662.

    Google Scholar 

  195. Mochizuki M, Maruo T. Effect of dehydroepiandrosterone sulfate on uterine cervical ripening in late pregnancy. Acta Physiol Hung. 1985;65(3):267–74.

    CAS  PubMed  Google Scholar 

  196. Rajabi M, Solomon S, Poole AR. Hormonal regulation of interstitial collagenase in the uterine cervix of the pregnant guinea pig. Endocrinology. 1991;128(2):863–71.

    CAS  PubMed  Google Scholar 

  197. Sato T, et al. Hormonal regulation of collagenolysis in uterine cervical fibroblasts. Modulation of synthesis of procollagenase, prostromelysin and tissue inhibitor of metalloproteinases (TIMP) by progesterone and oestradiol-17 beta. Biochem J. 1991;275(Pt 3):645–50.

    PubMed Central  CAS  PubMed  Google Scholar 

  198. Denison FC, Calder AA, Kelly RW. The action of prostaglandin E2 on the human cervix: stimulation of interleukin 8 and inhibition of secretory leukocyte protease inhibitor. Am J Obstet Gynecol. 1999;180(3 Pt 1):614–20.

    CAS  PubMed  Google Scholar 

  199. Carbonne B, et al. Effects of progesterone on prostaglandin E(2)-induced changes in glycosaminoglycan synthesis by human cervical fibroblasts in culture. Mol Hum Reprod. 2000;6(7):661–4.

    CAS  PubMed  Google Scholar 

  200. Elovitz MA, Mrinalini C. The use of progestational agents for preterm birth: lessons from a mouse model. Am J Obstet Gynecol. 2006;195(4):1004–10.

    CAS  PubMed  Google Scholar 

  201. Facchinetti F, et al. Cervical length changes during preterm cervical ripening: effects of 17-alpha-hydroxyprogesterone caproate. Am J Obstet Gynecol. 2007;196(5):453–4.

    PubMed  Google Scholar 

  202. Chwalisz K, Garfield RE. Regulation of the uterus and cervix during pregnancy and labor. Role of progesterone and nitric oxide. Ann N Y Acad Sci. 1997;828:238–53.

    CAS  PubMed  Google Scholar 

  203. Chwalisz K, et al. Cervical ripening in guinea-pigs after a local application of nitric oxide. Hum Reprod. 1997;12(10):2093–101.

    CAS  PubMed  Google Scholar 

  204. Chwalisz K, Garfield R. Nitric oxide as the final metabolic mediator of cervical ripening. Hum Reprod. 1998;13:245–52.

    CAS  PubMed  Google Scholar 

  205. Word RA, et al. Dynamics of cervical remodeling during pregnancy and parturition: mechanisms and current concepts. Semin Reprod Med. 2007;25(1):69–79.

    CAS  PubMed  Google Scholar 

  206. Stiemer B, Elger W. Cervical ripening of the rat in dependence on endocrine milieu; effects of antigestagens. J Perinat Med. 1990;18(6):419–29.

    CAS  PubMed  Google Scholar 

  207. Marx SG, et al. Effects of progesterone on iNOS, COX-2, and collagen expression in the cervix. J Histochem Cytochem. 2006;54(6):623–39.

    CAS  PubMed  Google Scholar 

  208. Chwalisz K, Garfield R. Antiprogestins in the induction of labor. Ann N Y Acad Sci. 1994;734:387–413.

    CAS  PubMed  Google Scholar 

  209. Elliott CL, Brennand JE, Calder AA. The effects of mifepristone on cervical ripening and labor induction in primigravidae. Obstet Gynecol. 1998;92(5):804–9.

    CAS  PubMed  Google Scholar 

  210. Stenlund PM, et al. Induction of labor with mifepristone–a randomized, double-blind study versus placebo. Acta Obstet Gynecol Scand. 1999;78(9):793–8.

    CAS  PubMed  Google Scholar 

  211. Giacalone PL, et al. The effects of mifepristone on uterine sensitivity to oxytocin and on fetal heart rate patterns. Eur J Obstet Gynecol Reprod Biol. 2001;97(1):30–4.

    CAS  PubMed  Google Scholar 

  212. Hegele-Hartung C, et al. Ripening of the uterine cervix of the guinea-pig after treatment with the progesterone antagonist onapristone (ZK 98.299): an electron microscopic study. Hum Reprod. 1989;4(4):369–77.

    CAS  PubMed  Google Scholar 

  213. Wolf JP, et al. Progesterone antagonist (RU 486) for cervical dilation, labor induction, and delivery in monkeys: effectiveness in combination with oxytocin. Am J Obstet Gynecol. 1989;160(1):45–7.

    CAS  PubMed  Google Scholar 

  214. Stys SJ, Clewell WH, Meschia G. Changes in cervical compliance at parturition independent of uterine activity. Am J Obstet Gynecol. 1978;130(4):414–8.

    CAS  PubMed  Google Scholar 

  215. Glassman W, Byam-Smith M, Garfield RE. Changes in rat cervical collagen during gestation and after antiprogesterone treatment as measured in vivo with light-induced autofluorescence. Am J Obstet Gynecol. 1995;173(5):1550–6.

    CAS  PubMed  Google Scholar 

  216. Imada K, et al. Hormonal regulation of matrix metalloproteinase 9/gelatinase B gene expression in rabbit uterine cervical fibroblasts. Biol Reprod. 1997;56(3):575–80.

    CAS  PubMed  Google Scholar 

  217. Imada K, et al. An antiprogesterone, onapristone, enhances the gene expression of promatrix metalloproteinase 3/prostromelysin-1 in the uterine cervix of pregnant rabbit. Biol Pharm Bull. 2002;25(9):1223–7.

    CAS  PubMed  Google Scholar 

  218. Granstrom L, Ekman G, Malmstrom A. Insufficient remodelling of the uterine connective tissue in women with protracted labour. Br J Obstet Gynaecol. 1991;98(12):1212–6.

    CAS  PubMed  Google Scholar 

  219. Osmers R, et al. Collagenase activity in the cervix of non-pregnant and pregnant women. Arch Gynecol Obstet. 1990;248(2):75–80.

    CAS  PubMed  Google Scholar 

  220. Danforth DN, Buckingham JC, Roddick Jr JW. Connective tissue changes incident to cervical effacement. Am J Obstet Gynecol. 1960;80:939–45.

    CAS  PubMed  Google Scholar 

  221. Winn RJ, Baker MD, Sherwood OD. Individual and combined effects of relaxin, estrogen, and progesterone in ovariectomized gilts. I. Effects on the growth, softening, and histological properties of the cervix. Endocrinology. 1994;135(3):1241–9.

    CAS  PubMed  Google Scholar 

  222. Clark K, et al. Mifepristone-induced cervical ripening: structural, biomechanical, and molecular events. Am J Obstet Gynecol. 2006;194(5):1391–8.

    CAS  PubMed  Google Scholar 

  223. Cabrol D, et al. Prostaglandin E2-induced changes in the distribution of glycosaminoglycans in the isolated rat uterine cervix. Eur J Obstet Gynecol Reprod Biol. 1987;26(4):359–65.

    CAS  PubMed  Google Scholar 

  224. Danforth DN, et al. The effect of pregnancy and labor on the human cervix: changes in collagen, glycoproteins, and glycosaminoglycans. Am J Obstet Gynecol. 1974;120(5):641–51.

    CAS  PubMed  Google Scholar 

  225. von Maillot K, et al. Changes in the glycosaminoglycans distribution pattern in the human uterine cervix during pregnancy and labor. Am J Obstet Gynecol. 1979;135(4):503–6.

    Google Scholar 

  226. Osmers R, et al. Glycosaminoglycans in cervical connective tissue during pregnancy and parturition. Obstet Gynecol. 1993;81(1):88–92.

    CAS  PubMed  Google Scholar 

  227. Cabrol D, et al. Induction of labor and cervical maturation using mifepristone (RU 486) in the late pregnant rat. Influence of a cyclooxygenase inhibitor (Diclofenac). Prostaglandins. 1991;42(1):71–9.

    CAS  PubMed  Google Scholar 

  228. Rechberger T, Woessner Jr JF. Collagenase, its inhibitors, and decorin in the lower uterine segment in pregnant women. Am J Obstet Gynecol. 1993;168(5):1598–603.

    CAS  PubMed  Google Scholar 

  229. Junqueira LC, et al. Morphologic and histochemical evidence for the occurrence of collagenolysis and for the role of neutrophilic polymorphonuclear leukocytes during cervical dilation. Am J Obstet Gynecol. 1980;138(3):273–81.

    CAS  PubMed  Google Scholar 

  230. Hertelendy F, Zakar T. Prostaglandins and the myometrium and cervix. Prostaglandins Leukot Essent Fatty Acids. 2004;70(2):207–22.

    CAS  PubMed  Google Scholar 

  231. Ramos JG, et al. Estrogen and progesterone modulation of eosinophilic infiltration of the rat uterine cervix. Steroids. 2000;65(7):409–14.

    CAS  PubMed  Google Scholar 

  232. Barclay CG, et al. Interleukin-8 production by the human cervix. Am J Obstet Gynecol. 1993;169(3):625–32.

    CAS  PubMed  Google Scholar 

  233. Baggiolini M, Walz A, Kunkel SL. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest. 1989;84(4):1045–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  234. Leonhardt SA, Boonyaratanakornkit V, Edwards DP. Progesterone receptor transcription and non-transcription signaling mechanisms. Steroids. 2003;68(10–13):761–70.

    CAS  PubMed  Google Scholar 

  235. Yen SSC. Endocrine-metabolic adaptation in pregnancy. In: Yen SSC, Jaffe RB, editors. Reproductive endocrinology. Philadelphia, PA: WB Saunders; 1991. p. 936–71.

    Google Scholar 

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Acknowledgment

This chapter was supported by the Intramural Research Program of the National Institute of Child Health and Human Development, NIH, DHHS.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Kaplan Medical Center, Rehovot, Israel

    Edi Vaisbuch

  2. Department of Obstetrics and Gynecology, Soroka Medical Center, Beer-Sheva, Israel

    Offer Erez

  3. Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, USA

    Roberto Romero M.D.

  4. Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA

    Roberto Romero M.D.

  5. Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA

    Roberto Romero M.D.

  6. Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA

    Roberto Romero M.D.

  7. Division of Intramural Research, Wayne State University/Hutzel Women’s Hospital, NICHD/NIH/DHHS, 3990 John R., Box #4, Detroit, MI, 48201, USA

    Roberto Romero M.D.

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  1. Edi Vaisbuch
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Correspondence to Roberto Romero M.D. .

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  1. Tel Aviv University, Tel Aviv, Tel Aviv, Israel

    Howard J.A. Carp

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Vaisbuch, E., Erez, O., Romero, R. (2015). Physiology of Progesterone. In: Carp, H. (eds) Progestogens in Obstetrics and Gynecology. Springer, Cham. https://doi.org/10.1007/978-3-319-14385-9_1

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