Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Local paracrine effects of estradiol are central to parturition in the rhesus monkey

Nature Medicine volume 4, pages 456–459 (1998)Cite this article

Abstract

The central biochemical mechanisms involved in primate parturition are still unclear. Studies in both humans and nonhuman primates such as the baboon and rhesus monkey indicate that many factors play a part in the cascade of interactive positive feedforward loops that progressively promote parturition: changes in maternal endocrinology, a nocturnal switch in myometrial activity from low amplitude, infrequent contractures to high amplitude, high frequency contractions (see Fig. 1), dilation of the cervix and biochemical changes in the fetal membranes that lead to rupture1. Here we demonstrate that infusion of the aromatase inhibitor 4-hydroxyandrostenedione (40HA) inhibits conversion of androgen to estrogen and prevents premature delivery caused by administration of androgen to pregnant rhesus monkeys at 0.8 of pregnancy term. 4OHA also inhibited the androstenedione induced maternal endocrine and fetal membrane biochemical changes, and alteration of myometrial activity patterns. Secondly, peripheral estrogen infusions increased myometrial activity but did not produce preterm delivery or fetal membrane changes. We conclude that paracrine functions of estrogen at its site of production play critical and central roles in delivery in the non-human primate.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Olson, D.M., Mijovic, J.E. & Sadowsky, D.W. Control of human parturition. Semin. Perinatal. 19, 52–63 (1995).

    Article  CAS  Google Scholar 

  2. Magyar, D.M. et al. Time-trend analysis of plasma cortisol concentrations in the fetal sheep in relation to parturition. Endocrinology 107, 155–159 (1980).

    Article  CAS  Google Scholar 

  3. Steele, P.W., Flint, A.P.F. & Turnbull, A.C. Activity of steroid C-17,20 lyase in the ovine placenta: effect of exposure to foetal glucocorticoid. J. Endocrinol. 69, 239–246 (1976).

    Article  CAS  Google Scholar 

  4. Nathanielsz, P.W. et al. Time trend analysis of plasma unconjugated and sulfocon-jugated estrone and 3β–Δ5 - steroids in fetal and maternal sheep plasma in relation to spontaneous parturition at term. Endocrinology 110, 1402–1407 (1982).

    Article  CAS  Google Scholar 

  5. Challis, J.R.G. Sharp increase in free circulating oestrogens immediately before parturition in sheep. Nature 229, 208 (1971).

    Article  CAS  Google Scholar 

  6. Eisner, C.W. et al. Time-trend analysis of plasma C-21 steroids in fetal and maternal sheep during the last 18 days of gestation. Endocrinology 107, 801–808 (1980).

    Article  Google Scholar 

  7. Novy, M.J. & Walsh, S.W. Regulation of fetoplacental steroidogenesis in rhesus macaques. In Fetal Endocrinology (Novy M.J. and Resko, J.A., eds), 66-94 (Academic Press, NY, (1981).

    Google Scholar 

  8. Wilson, L., Parsons, M.T. & Flouret, C. Forward shift in the initiation of the nocturnal estradiol surge in the pregnant baboon: Is this the genesis of labor?. Am. I. Obstet. Cynecol. 165, 1487–1498 (1991).

    Article  CAS  Google Scholar 

  9. Buster, J.E. et al. Interrelationships of circulating maternal steroid concentrations in third trimester pregnancies. I. C21 steroids: Progesterone, 16α-hydroxyproges-terone, 17α-hydroxyprogesterone, 20α-dihydroprogesterone, Δ5-pregnenolone, Δ5-pregnenolone sulfate, and 17-hydroxy Δ5-pregnenolone. J. Clin. Endo. Metab. 48, 133–138 (1979).

    Article  CAS  Google Scholar 

  10. Siiteri, P.K. & Seron-Ferre, M. Some new thoughts on the fetoplacental unit and parturition in primates. In Fetal Endocrinology. (Novy, M.J. and Resko, J.A, eds.), 1-34 (Academic Press, NY, 1981).

    Google Scholar 

  11. Buster, J.E. et al. Interrelationships of circulating maternal steroid concentrations in third trimester pregnancies II. C18 and C19 steroids: estradiol, estriol, dehydroepiandrosterone, dehydroepiandrosterone sulfate, 5-androstenediol, 4-an-drostenedione, testosterone, and dihydrotestosterone. J. Clin. Endo. Metab. 48, 139–142 (1979).

    Article  CAS  Google Scholar 

  12. Lye, S.J., Nicholson, B.J., Mascarenhas, M., MacKenzie, L. & Petrocelli, T. Increased expression of connexin-43 in the rat myometrium during labor is associated with an increase in the plasma estrogen: Progesterone ratio. Endocrinology 132, 2380–2386 (1993).

    Article  CAS  Google Scholar 

  13. Amico, J.A., Janosky, J.E. & Cameron, J.L. Effect of estradiol and progesterone administration upon the circadian rhythm of oxytocin in the cerebrospinal fluid of rhesus monkeys. Neuroendocrinology 51, 543–551 (1990).

    Article  CAS  Google Scholar 

  14. Zhang, P.G., Weston & Hixon, J.E. Influence of estradiol on the secretion of oxytocin and prostaglandin F2α2 during luteolysis in the ewes. Biol. Reprod. 45, 395–403 (1991).

    Article  CAS  Google Scholar 

  15. Petrocelli, T. & Lye, S.J. Regulation of transcripts encoding the myometrial gap junction protein, connexin-43, by estrogen and progesterone. Endocrinology 133, 284–290(1993).

    Article  CAS  Google Scholar 

  16. Wu, W.X., Owiny, J.R., Zhang, Q., Ma, X.H. & Nathanielsz, P.W. Regulation of the estrogen receptor and its mRNA in the ovariectomized sheep myometrium and en-dometrium: The role of estradiol and progesterone. Biol. Reprod. 555, 762–768 (1996).

    Google Scholar 

  17. J.,Daren, McGarrigl, C.L. & Lachelin,, G.C.L Increased saliva oestriol to progesterone ratio before idiopathic preterm delivery: a possible predictor for preterm labour. Br. Med. J. 294, 270–272 (1987).

    Article  Google Scholar 

  18. Germain, A.M., Kato, S., Villarroel, L.A., Valenzuela, G.J. & Seron-Ferre, M. Human term and preterm delivery is preceded by a rise in maternal plasma 17-estradiol. Prenatal & Neonatal Med. 1, 57–63 (1996).

    Google Scholar 

  19. Haluska, G.J., Cook, M.J. & Novy, M.J. Inhibition and augmentation of progesterone production during pregnancy: Effects on parturition in rhesus monkeys. Am. J. Obstet. Cynecol. 176, 682–691 (1997).

    Article  CAS  Google Scholar 

  20. Mecenas, C.A. et al. Production of premature delivery in pregnant rhesus monkeys by androstenedione infusion. Nature Med. 2,(4) 443–448 (1996).

    Article  CAS  Google Scholar 

  21. Amico, J.A. & Hempel, J. An oxytocin precursor intermediate circulates in the plasma of humans and rhesus monkeys administered estrogen. Neuroendocrinology 51, 437–443 (1990).

    Article  CAS  Google Scholar 

  22. Novy, M.J. & Walsh, S.W. Dexamethasone and estradiol treatment in pregnant rhesus macaques: Effects on gestational length, maternal plasma hormones, and fetal growth. Am. J. Obstet. Cynecol. 145, 920–931 (1983).

    Article  CAS  Google Scholar 

  23. Cibbar, R., Wong, S., Miller, F.D. & Mitchell, B.F. Estrogen stimulates oxytocin gene expression in human chorio-decidua. J. Clin. Endo. Metab. 80, 567–572 (1995).

    Google Scholar 

  24. Lefebvre, D.L., Farookhi, R., Giaid, A., Neculcea, J. & Zingg, H.H. Uterine oxytocin gene expression. II. induction by exogenous steroid administration. Endocrinology 134, 2562–2566 (1994).

    Article  CAS  Google Scholar 

  25. Farber, D.M. et al Timing of the switch from myometrial contractures to contractions in late-gestation pregnant rhesus monkeys as recorded by myometrial electromyogram during spontaneous term and androstenedione-induced labor. Biol. Reprod. 56, 557–562 (1997).

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Peter W. Nathanielsz: Correspondence should be addressed to P.W.N.

Authors and Affiliations

  1. Laboratory for Pregnancy and Newborn Research, College of Veterinary Medicine, Dept. Physiology, Cornell University, Ithaca, NY, 14853-6401

    Peter W. Nathanielsz, Susan L. Jenkins, Jennifer D. Tame, James A. Winter, Seth Guller & Dino A. Giussani

  2. Deptartment Obstetrics & Gynecology, NYU Medical Center, New York, NY 10016

    Seth Guller

Authors
  1. Peter W. Nathanielsz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susan L. Jenkins
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jennifer D. Tame
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. James A. Winter
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Seth Guller
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dino A. Giussani
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nathanielsz, P., Jenkins, S., Tame, J. et al. Local paracrine effects of estradiol are central to parturition in the rhesus monkey. Nat Med 4, 456–459 (1998). https://doi.org/10.1038/nm0498-456

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm0498-456

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing