New Perspectives on Estrogen, Progesterone, and Oxytocin Action in Primate Parturition

  • Miles J. Novy
  • George J. Haluska
Conference paper
Part of the Ernst Schering Research Foundation Workshop book series (SCHERING FOUND, volume 7)


In studying the control of parturition in primates it is logical to concentrate on those endocrine and paracrine regulators which have proven to be important prerequisites for parturition in other species (i.e., estrogens, progesterone, prostaglandins, oxytocin, and cytokines). It has been shown in domestic ruminants that increased estrogen levels and falling progesterone levels at term (dependent upon the fetal adrenal secretion of Cortisol) are pivotal for the initiation of parturition (Liggins et al. 1977; Challis and Olson 1988). Although the rising production of estrogens by the fetoplacental unit provides an attractive mechanism for the endocrine initiation of labor in primates, estrogens likely serve only a permissive function in parturition. There is no evidence for the lowering of progesterone concentrations in the maternal, fetal, or amniotic fluid compartments in higher primates prior to or during labor. However, a prepartum fall in progesterone is such a ubiquitous phenomenon across species that it is still tempting to search for evidence of a localized progesterone withdrawal mechanism in target tissues of primates. Indeed, the recent availability of effective antiprogestins has provided an efficient tool to facilitate such investigation.


Rhesus Monkey Maternal Plasma Fetal Membrane Spontaneous Labor Cervical Ripening 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Amico JA, Seif SM, Robinson AG (1981) Oxytocin in human plasma: correlation with neurophysin and stimulation with estrogen. J Clin Endocrinol Metab 52:988–993PubMedCrossRefGoogle Scholar
  2. Bowden D, Winter P, Ploog G (1967) Pregnancy and delivery behavior in the squirrel monkey (Saimri sciureus) and other primates. Folia Primatol (Basel) 5:1–42CrossRefGoogle Scholar
  3. Brandt EM, Mitchell G (1971) Parturition in primates: behavior related to birth. In: Rosenblum LA (ed) Primate Behavior Development in Field and Laboratory Research. Academic Press, New York, pp 177–183Google Scholar
  4. Brenner RM, West NB, McClellan MC (1990) Estrogen and progestin receptors in the reproductive tract of male and female primates. Biol Reprod 42:11–19PubMedCrossRefGoogle Scholar
  5. Calder AA (1990) Control of Parturition: Scientific and Clinical Aspects. In: Garfield RE (ed) Uterine Contractility, Serono Symposia, USA, Massachusetts, pp 283–293Google Scholar
  6. Challis JRG, Olson DM (1988) Parturition. In: Knobil E, Neill J (eds) The Physiology of Reproduction, Raven Press, New York, pp 2177–2216Google Scholar
  7. Challis JRG, Sprague C, Patrick JE (1983) Relation between diurnal changes in peripheral plasma progesterone, Cortisol, and estriol in normal women at 30–31, 34–35, and 28–29 weeks of gestation. Gynecol Obstet Invest 16:33–44PubMedCrossRefGoogle Scholar
  8. Chibbar R, Miller FD, Mitchell BF (1993) Synthesis of oxytocin in amnion, chorion, and decidua may influence the timing of human parturition. J Clin Invest 91:185–192PubMedCrossRefGoogle Scholar
  9. Couzinet B, Le Strat N, Ulmann A, Baulieu EE, Schaison G (1986) Termination of early pregnancy by the progesterone antagonist RU486 (mifepristone). N Engl J Med 315:1656–1670CrossRefGoogle Scholar
  10. Doyle GA, Pelletied A, Bekkeer T (1967) Courtship, mating and parturition in the lesser bushbaby (Balago senegalensis moboli) under semi-natural conditions. Folia Primatol (Basel) 7:169–197CrossRefGoogle Scholar
  11. Ducsay CA, Cook MJ, Walsh SW, Novy MJ (1983) Circadian patterns and dexamethasone-induced changes in uterine activity in pregnant rhesus monkeys. Am J Obstet Gynecol 145:389–396PubMedGoogle Scholar
  12. Ducsay CA, Yellon SM (1991) Photoperiod regulation of uterine activity and melatonin rhythms in the pregnant rhesus macaque. Biol Reprod 44:967–974PubMedCrossRefGoogle Scholar
  13. Figueroa JP, Honnebier MBOM, Binienda Z, Wimsatt J, Nathanielsz PW (1989) Effect of 48-hour intravenous D4-androstenedione infusion on the pregnant rhesus monkey in the last third of gestation: Changes in maternal plasma estradiol concentrations and myometrial activity. Am J Obstet Gynecol 161:481–486PubMedCrossRefGoogle Scholar
  14. Figueroa JP, Honnebier MBOM, Jenkins S, Nathanielsz PW (1990) Alteration of 24 h rhythms in myometrial activity in the chronically catheterized pregnant rhesus monkey following a 6 h shift in the light-dark cycle. Am J Obstet Gynecol 163:648PubMedCrossRefGoogle Scholar
  15. Frydman R, Lelaidier C, Baton-Saint-Mleux C, Fernandez H, Vial M, Bourget P (1992) Labor induction in women at term with mifepristone (RU486): A double-blind, randomized, placebo-controlled study. Obstet Gynecol 80:972–975PubMedGoogle Scholar
  16. Fuchs AR (1986) The role of oxytocin in parturition. In: Huszar G (ed) The Physiology and Biochemistry of the Uterus in Pregnancy and Labor. CRC Press, Boca Raton, FL pp 163–183Google Scholar
  17. Fuchs AR, Behrens O, Liu H-C (1992) Correlation of nocturnal increase in plasma oxytocin with a decrease in plasma estradiol/progesterone ratio in late pregnancy. Am J Obstet Gynecol 167:1559–1563PubMedCrossRefGoogle Scholar
  18. Fuchs AR, Goeschen K, Husslein P, Rasmussen AB, Fuchs F (1983) Oxytocin and the initiation of human parturition. III. Plasma concentrations of oxytocin an d13,14-dihydro-15-keto-prostaglandin F2a in spontaneous and oxytocin-induced labor at term. Am J Obstet Gynecol 147:497–502PubMedGoogle Scholar
  19. Garfield RE, Gasc JM, Baulieu MD (1987) Effects of the antiprogesterone RU486 on preterm birth in the rat. Am J Obstet Gynecol 157:1281–1285PubMedGoogle Scholar
  20. Garfield RE, Kannan MS, Daniel EE (1980) Gap junction formation in myometrium: control by estrogens, progesterone, and prostaglandins. Am J Physiol 238:C81–C89Google Scholar
  21. Garfield RE, Tabb T, Thilander G (1990) Intercellular coupling and modulation of uterine contractility. In: Garfield RE (ed) Uterine Contractility, Serono Symposia, USAGoogle Scholar
  22. Germain AM, Valenzuela GJ, Ivanhovic M, Ducsay CA, Gabella C, Seron-Ferre M (1993) Relationship of circadian rhythms of uterine activity with term and preterm delivery. Am J Obstet Gynecol 168:1271–1277PubMedCrossRefGoogle Scholar
  23. Germain G, Cabrol D, Visser A, Sureau C (1982) Electrical activity of the pregnant uterus in the cynomolgus monkey. Am J Obstet Gynecol 142:513–518PubMedGoogle Scholar
  24. Germain G, Lopes P, Cabrol D, Barbe MP, Huneau D, le Houezec R, Sureau C (1986) A comparison of uterine motility in the pregnant and nonpregnant cynomolgus monkesy (Macaca fascicularis) and pregnant women: A man-ometric and electromyographic study. Acta Physiol Hung 67:95–115PubMedGoogle Scholar
  25. Germain G, Philibert D, Pottier J, Mouren M, Baulieu EE, Sureau C (1985) Effects of the antiprogesterone agent RU486 on the natural cycle and gestation in the intact cynomolgus monkeys. In: Baulieu EE, Segal SJ (eds) The Antiprogesterone Steroid RU486 and Human Fertility Control. Plenum Press, New York, pp 155–168CrossRefGoogle Scholar
  26. Giannopoulos G, Jackson K, Tulchinsky D (1983) Specific glucocorticoid binding in human uterine tissues, placenta and fetal membranes. J Steroid Biochem 19:1375PubMedCrossRefGoogle Scholar
  27. Gibb W (1977) Steroid modulation by the human fetal membranes. In: Second Symposia publications, The Endocrine Physiology of Pregnancy and the Peripartal Period, Raven Press, New York, p 135Google Scholar
  28. Haluska GJ, Cook MJ, Novy MJ (1988) Prostaglandin production by intrauterine tissues of the rhesus monkey after RU486 treatment. Biol Reprod 38 [suppl 1]: abstract 266Google Scholar
  29. Haluska GJ, Cook MJ, Novy MJ (1991) Epostane but not RU486 mimics spontaneous parturition in rhesus monkeys. Soc Gynecol Invest, San Antonio TX, abstract 11Google Scholar
  30. Haluska GJ, Cook MJ, Novy MJ (1993) Effect of onapristone (ZK98299) on uterine activity an cervical status in late gestation rhesus monkeys. Soc Gynecol Invest, Toronto, Ontario, abstract S24Google Scholar
  31. Haluska GJ, Cook MJ, Witkin SS, Novy MJ (1992) Epostane induces parturition in rhesus monkeys by lowering endogenous progesterone concentrations. In: Soc Gynecol Invest, San Antonio TX, abstract 244Google Scholar
  32. Haluska GJ, Jay IC, Novy MJ (1989) Gap junctions in the primate myometrium: effect of RU486. Biol Reprod 40 [Suppl 1] abstract 250CrossRefGoogle Scholar
  33. Haluska GJ, Mitchell MD, Novy MJ (1990b) Amniotic fluid lipoxygenase metabolites during spontaneous labor and after RU486 treatment during late pregnancy in rhesus macaques. Prostaglandins 40:99–105PubMedGoogle Scholar
  34. Haluska GJ, Stanczyk FZ, Cook MJ, Novy MJ (1987) Temporal changes in uterine activity and progesterone response to RU486 in rhesus macaques in late gestation. Am J Obstet Gynecol 157:1487–1495PubMedGoogle Scholar
  35. Haluska GJ, West NB, Novy MJ, Brenner RM (1990a) Uterine estrogen receptors are increased by RU486 in late pregnant rhesus macaques but not after spontaneous labor. J Clin Endocrinol Metab 70:181–186PubMedCrossRefGoogle Scholar
  36. Harbert GM (1977) Biorhythms of the pregnant utereus (Macaca mulatto). Am J Obstet Gynecol 129:401–408PubMedGoogle Scholar
  37. Harbert GM, Spisso KR (1980) Biorhythms of the primate uterus (Macaca mulatto) during labor and delivery. Am J Obstet Gynecol 138:686–692PubMedGoogle Scholar
  38. Hess DL, Spies HG, Hendrickx AG (1981) Diurnal steroid patterns during gestation in the rhesus macaque: Onset, daily variation and the effects of dexamethasone treatment. Biol Reprod 24:609–616PubMedCrossRefGoogle Scholar
  39. Hill NCW, Selinger M, Ferguson J, Lopez-Bernal A, MacKenzie IZ (1990) The physiological and clinical effects of progesterone inhibition with mifepristone (RU486) in the second trimester. Br J Obstet Gynecol 97:487–192CrossRefGoogle Scholar
  40. Hirst JJ, West NB, Brenner RM, Novy MJ (1990) Myometrial and decidual progesterone receptors during gestation, in spontaneous labor and after RU486 treatment in rhesus monkeys. In: Proceedings of the Serono Symposium on Uterine Contractility: Mechanisms of Control, St. Louis, Missouri, p 41, abstract 17Google Scholar
  41. Hirst JJ, Haluska GJ, Cook MJ, Hess DL, Novy MJ (1991a) Comparison of plasma oxytocin and catecholamine concentrations with uterine activity in pregnant rhesus monkeys. J Clin Endocrinol Metab 73:804–810PubMedCrossRefGoogle Scholar
  42. Hirst JJ, Haluska GJ, Cook MJ, Novy MJ (1991b) Maternal plasma oxytocin (OT) and oxytocin receptor concentrations during late pregnancy in rhesus monkeys. In: Proceedings of the 38th annual meeting of the Society for Gynecologic Investigation, San Antonio, TX, p 146Google Scholar
  43. Hirst JJ, Haluska GJ, Cook MJ, Novy MJ (1993) Plasma oxytocin and nocturnal uterine activity: Maternal but not fetal concentrations increase progressively during late pregnancy and delivery in rhesus monkeys. Am J Obstet Gynecol 169:414–422CrossRefGoogle Scholar
  44. Honnebier MBOM, Figueroa JP, Nathanielsz PW (1989a) Variation in myometrial response to pulsatile intravenous oxytocin administration — a pulsatile oxytocin challenge test at different times of the day in the pregnant rhesus monkey at 121 to 138 days gestational age. Endocrinology 125:1498–1503PubMedCrossRefGoogle Scholar
  45. Honnebier MBOM, Figueroa JP, Rivier J, Vale W, Nathanielsz PW (1989b) Studies of the role of oxytocin in late pregnancy in the pregnant rhesus monkey: plasma concentrations of oxytocin in the maternal circulation throughout the 24-h day and the effect of the synthetic oxytocin antagonist [1-B-Mpa (B-(CH2)5)l,(Me(Tyr2,Orn8] oxytocin. J Dev Physiol 12:225–232PubMedGoogle Scholar
  46. Honnebier MBOM, Jenkins SL, Wentworth RA, Figueroa JP, Nathanielsz PW (1991) Temporal structural of delivery in the absence of a photoperiod: Preparturient myometrial activity of the rhesus monkey is related to maternal body temperature and depends on the maternal circadian system. Biol Reprod 45:617–625PubMedCrossRefGoogle Scholar
  47. Honnebier MBOM, Jenkins SL, Nathanielsz PW (1992) Circadian timekeeping during pregnancy: endogenous phase relationships between maternal plasma hormones and the maternal body temperature rhythm in pregnant rhesus monkeys. Endocrinology 131:2051–2058PubMedCrossRefGoogle Scholar
  48. Husslein P, Fuchs AR, Fuchs F (1981) Oxytocin and the initiation of human parturition. I. Prostaglandin release during induction of labor by oxytocin. Am J Obstet Gynecol 141:688–393PubMedGoogle Scholar
  49. Ito A, Hiro D, Ojima Y, Mori Y (1988) Spontaneous production of inter-leukin-1-like factors from pregnant rabbit uterine cervix. Am J Obstet Gynecol 159:261–265PubMedGoogle Scholar
  50. Jensen GD, Bobbitt RA (1967) Changing parturition time in monkeys (Macaca nemistrina) from night to day. Lab Anim Care 17:379–381PubMedGoogle Scholar
  51. Klein-Hitpass L, Cato ACB, Henderson D, Ryffel GU (1991) Two types of antiprogestins identified by their differential action in transcriptionally active extracts from T47D cells. Nucleic Acid Res 19:1227–1234PubMedCrossRefGoogle Scholar
  52. Kocan LH, MacLusky NJ, Lye SJ (1993) Dexamethasone reverses the labor-associated myometrial desensitization to β adrenergic agonists in the rat. Am J Obstet Gynecol 168:961–968PubMedCrossRefGoogle Scholar
  53. Liggins GC, Fairclough RJ, Grieves SA, Forster CS, Knox BS (1977) Parturition in the sheep. In: Knight J, O’Connor M (eds) The fetus and birth. Ciba Found Symp 47:5Google Scholar
  54. Longo LD, Yellon SM (1988) Biological timekeeping during pregnancy and the role of circadian rhythms in parturition. In: Kunzel W, Jensen A (eds) Endocrine Control of the Fetus. Springer, Berlin Heidelberg New York, pp 173–192CrossRefGoogle Scholar
  55. Main DM, Grisso JA, Wold T, Snyder ES, Holmes J, Chiu G (1991) Extended longitudinal study of uterine activity among low-risk women. Am J Obstet Gynecol 165:1317–1322PubMedGoogle Scholar
  56. Matsumoto T, Hess DL, Kaushal KM, Valenzuela GY, Yellon SM, Ducsay CA (1991) Circadian myometrial and endocrine rhythms in the pregnant rhesus macaque: Effects of constant light and timed melatonin infusion. Am J Obstet Gynecol 165:1777–1784PubMedCrossRefGoogle Scholar
  57. Mitchell B, Cruickshank B, McLean D, Challis JRG (1982) Local modulation of progesterone production in human fetal membranes. J Clin Endocrinol Metab 55:1237–1239PubMedCrossRefGoogle Scholar
  58. Mitchell MD, Brennecke SP, Novy MJ (1984) Prostaglandin synthease inhibitor activity in the plasma of rhesus monkeys during late pregnancy: Effect of dexamethasone. Prostaglandins Leukotrienes Med 14:199–204CrossRefGoogle Scholar
  59. Novy MJ, Haluska GJ (1988) Endocrine and paracrine control of parturition in rhesus monkeys. In: McNellis D, Challis JRG, MacDonald PC, Nathanielsz PW, Roberts JM (eds) The Onset of Labor: Cellular and Integrative Mechanisms, Perinatology Press, Ithaca, NY pp 321–337Google Scholar
  60. Novy MJ, Liggins GC (1980) Role of prostaglandins, prostacyclin, and thromboxanes in the physiologic control of the uterus and in parturition. Sem Perinatol 4:45–66Google Scholar
  61. Novy MJ, Walsh SW (1981) Regulation of fetoplacental steriodogenesis in rhesus macaques. In: Novy M J, Resko JA (eds) Fetal endocrinology. Academic, New York, pp 65–94Google Scholar
  62. Novy MJ, Walsh SW (1983) Dexamethasone and estradiol treatment in pregnant rhesus macaques: Effects on gestational length, maternal plasma hormones, and fetal growth. Am J Obstet Gynecol 145:920–931PubMedGoogle Scholar
  63. Novy MJ, Walsh SW, Cook MJ (1980) Chronic implantation of catheters and electrodes in pregnant nonhuman primates. In: Nathanielsz PW (ed) Animal Models in Fetal Medicine, Elsevier/North-Holland Biomedical Press, Amsterdam, p 133Google Scholar
  64. Novy MJ, Haluska GJ, Cook MJ (1989) Circadian uterine activity is abolished by fetal death but restored by maternal estradiol (E2) administration. In: Soc Gynecol Invest, San Diego CA, abstract 342Google Scholar
  65. Ogle TF (1986) Evidence for nuclear processing of progesterone receptors in rat placenta. J Steroid Biochem 25:183PubMedCrossRefGoogle Scholar
  66. Potestio FA, Zakar T, Olson DM (1988) Glucocorticoids stimulate prostaglandin synthesis in human amnion cells by a receptor-mediated mechanism. J Clin Endocrinol Metab 67:1205–1210PubMedCrossRefGoogle Scholar
  67. Quartero HWP, Fry CH (1989) Placental corticotrophin-releasing factor may modulate human parturition. Placenta 10:439–443PubMedCrossRefGoogle Scholar
  68. Rodger MW, Baird DT (1990) Pretreatment with mifepristone (RU486) reduces interval between prostaglandin administration and expulsion in second trimester abortion. Br J Obstet Gynecol 97:41–45CrossRefGoogle Scholar
  69. Shepherd RW, Stanczyk FZ, Bethea CL, Novy MJ (1992) Fetal and maternal endocrine responses to reduced uteroplacental blood flow. J Clin Endocrinol Metab 75:301–307PubMedCrossRefGoogle Scholar
  70. Siiteri PK, Serón-Ferré (1981) Some new thoughts on the fetoplacental unit and parturition in primates. In: Novy MJ, Resko JA (eds) Fetal Endocrinology, Academic Press, New York, pp 1–34Google Scholar
  71. Stanczyk FZ, Hess DL, Namkung PC, Senner JW, Petra PH, Novy MJ (1986) Alterations in sex steroid-binding protein (SBP), corticosteroid-binding globulin (CBG), and steroid hormone concentrations during pregnancy in rhesus macaques. Biol Reprod 35:126–132PubMedCrossRefGoogle Scholar
  72. Tambyraja RL, Hobel CJ (1983) Characterization of 24 hr uterine activity (UA) in the second half of the human pregnancy. Proceedings of the 30th annual meeting of the Society for Gynecologic Investigation, Washington DC, abstract 516Google Scholar
  73. Taylor NF, Martin MC, Nathanielsz PW, Serón-Ferré M (1983) The fetus determines circadian oscillation of myometrial electromyographic activity in the pregnant rhesus monkey. Am J Obstet Gynecol 146:557–567PubMedGoogle Scholar
  74. Walsh SW, Kittinger GW, Novy MJ (1979) Maternal peripheral concentrations of estradiol, estrone, Cortisol, and progesterone during late pregnancy in rhesus monkeys (Macaca mulatto) and after experimental fetal anencephaly and fetal death. Am J Obstet Gynecol 135:37–42PubMedGoogle Scholar
  75. Walsh SW, Ducsay CA, Novy MJ (1984a) Circadian hormonal interactions among the mother, fetus, and amniotic fluid. Am J Obstet Gynecol 150:745–753PubMedGoogle Scholar
  76. Walsh SW, Norman RL, Novy MJ (1979) In utero regulation of rhesus monkey fetal adrenals: Effects of dexamethasone, adrenocorticotropin, thyrotropin-releasing hormone, prolactin, human chorionic gonadotropin, and α-melanocyte-stimulating hormone on fetal and maternal plasma steroids. Endocrinology 104:1805–1813PubMedCrossRefGoogle Scholar
  77. Walsh SW, Stanczyk FZ, Novy MJ (1984b) Daily hormonal changes in the maternal, fetal and amniotic fluid compartments before parturition in a primate species. J Clin Endocrinol Metab 58:629–639PubMedCrossRefGoogle Scholar
  78. Wilson L, Parsons MT, Flouret G (1991) Forward shift in the initiation of the nocturnal estradiol surge in the pregnant baboon: Is this the genesis of labor. Am J Obstet Gynecol 165:1487–1498PubMedGoogle Scholar
  79. Wolf JP, Sinosich M, Anderson TL, Ulmann A, Baulieu EE, Hodgen GD (1989) Progesterone antagonist (RU486) for cervical dilation, labor induction, and delivery in monkeys: Effectiveness in combination with oxytocin. Am J Obstet Gynecol 160:45–47PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • Miles J. Novy
  • George J. Haluska

There are no affiliations available

Personalised recommendations