Endocrinology, Vol 137, 3213-3219, Copyright © 1996 by Endocrine Society

ARTICLES

Relationships among sex steroids, oxytocin, and their receptors in the rat uterus during late gestation and at parturition

X Fang, S Wong and BF Mitchell
Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Canada.

Sex steroids and oxytocin (OT) produced within intrauterine tissues have been implicated in the regulation of parturition. The purpose of these studies was 1) to determine the relationships among estradiol (E2), progesterone (P4), OT, and their receptors in uterine tissues during late gestation and parturition in the rat; 2) to observe the effects of the estrogen antagonist tamoxifen (TAM) on these factors; and 3) to evaluate the rat as a potential model for events at human parturition. Concentrations of E2, P4, PGE2, and OT were measured by RIA. E2 receptor (ER) was measured by enzyme immunoassay, and P4 receptor (PR) and OT receptor (OTR) were measured by binding assays. OT messenger RNA (mRNA) was measured by ribonuclease protection assay. Groups (n = 5) of pregnant rats (normal gestation = 22 days) were treated with TAM (200 mg/day) or vehicle and killed on gestation day 19, 21, 21.5, or 22 or after delivery of the first pup. Serum E2 increased throughout late gestation accompanied by an increase in uterine OT mRNA and ER. Serum P4 declined after day 19, and uterine PR did not change significantly. Uterine PGE2 increased progressively, reaching peak levels the evening before delivery. Uterine OTR did not increase until the morning of delivery, and uterine OT peptide concentrations increased only during parturition. Parturition was significantly delayed by 24 h in the TAM-treated group. TAM inhibited the increase in serum E2, uterine ER, and OT mRNA and peptide, but had no effect on serum P4 or uterine PR levels. With TAM, the responses of uterine OTR and PGE2 were significantly delayed, but still underwent a significant increase before the delayed parturition. These results support the hypothesis that E2 stimulates the synthesis of ER, OT, and OTR within the rat uterus and is essential for normal parturition. P4 withdrawal may be more important to the increases in OTR and PGE2, but these are delayed in the absence of estrogen. These data also suggest that the rat may be a relevant model for human parturition.

This article has been cited by other articles:

				Z. Zeng, M. C. Velarde, F. A. Simmen, and R. C.M. Simmen Delayed Parturition and Altered Myometrial Progesterone Receptor Isoform A Expression in Mice Null for Kruppel-Like Factor 9 Biol Reprod, June 1, 2008; 78(6): 1029 - 1037. [Abstract] [Full Text] [PDF]

				M. J Wentz, S.-Q. Shi, L. Shi, S. A Salama, H. M Harirah, H. Fouad, R. E Garfield, and A. Al-Hendy Treatment with an inhibitor of catechol-O-methyltransferase activity reduces preterm birth and impedes cervical resistance to stretch in pregnant rats Reproduction, December 1, 2007; 134(6): 831 - 839. [Abstract] [Full Text] [PDF]

				M. G. Farina, S. Billi, G. Leguizamon, C. Weissmann, T. Guadagnoli, M. L. Ribeiro, and A. M. Franchi Secretory and cytosolic phospholipase A2 activities and expression are regulated by oxytocin and estradiol during labor Reproduction, August 1, 2007; 134(2): 355 - 364. [Abstract] [Full Text] [PDF]

				C. R. Blystone, C. S. Lambright, K. L. Howdeshell, J. Furr, R. M. Sternberg, B. C. Butterworth, E. J. Durhan, E. A. Makynen, G. T. Ankley, V. S. Wilson, et al. Sensitivity of Fetal Rat Testicular Steroidogenesis to Maternal Prochloraz Exposure and the Underlying Mechanism of Inhibition Toxicol. Sci., June 1, 2007; 97(2): 512 - 519. [Abstract] [Full Text] [PDF]

				V. Terzidou, Y. Lee, T. Lindstrom, M. Johnson, S. Thornton, and P. R. Bennett Regulation of the Human Oxytocin Receptor by Nuclear Factor-{kappa}B and CCAAT/Enhancer-Binding Protein-{beta} J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2317 - 2326. [Abstract] [Full Text] [PDF]

				A L Griffiths, K M Marshall, J Senior, C Fleming, and D F Woodward Effect of the oestrous cycle, pregnancy and uterine region on the responsiveness of the isolated mouse uterus to prostaglandin F2{alpha} and the thromboxane mimetic U46619. J. Endocrinol., March 1, 2006; 188(3): 569 - 577. [Abstract] [Full Text] [PDF]

				A. Parizek, M. Hill, R. Kancheva, H. Havlikova, L. Kancheva, J. Cindr, A. Paskova, V. Pouzar, I. Cerny, P. Drbohlav, et al. Neuroactive Pregnanolone Isomers during Pregnancy J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 395 - 403. [Abstract] [Full Text] [PDF]

				V. Terzidou, S. R. Sooranna, L. U. Kim, S. Thornton, P. R. Bennett, and M. R. Johnson Mechanical Stretch Up-Regulates the Human Oxytocin Receptor in Primary Human Uterine Myocytes J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 237 - 246. [Abstract] [Full Text] [PDF]

				S. Dogan, D. A. Deshpande, M. S. Kannan, and T. F. Walseth Changes in CD38 Expression and ADP-Ribosyl Cyclase Activity in Rat Myometrium During Pregnancy: Influence of Sex Steroid Hormones Biol Reprod, July 1, 2004; 71(1): 97 - 103. [Abstract] [Full Text] [PDF]

				A. L. Siebel, H. M. Gehring, I. G. T. Reytomas, and L. J. Parry Inhibition of Oxytocin Receptor and Estrogen Receptor-{alpha} Expression, But Not Relaxin Receptors (LGR7), in the Myometrium of Late Pregnant Relaxin Gene Knockout Mice Endocrinology, October 1, 2003; 144(10): 4272 - 4275. [Abstract] [Full Text] [PDF]

				X. Fang, S. Wong, and B. F. Mitchell Messenger RNA for progesterone receptor isoforms in the late-gestation rat uterus Am J Physiol Endocrinol Metab, December 1, 2002; 283(6): E1167 - E1172. [Abstract] [Full Text] [PDF]

				A. L. Siebel, H. M. Gehring, and L. J. Parry Effects of Fetectomy on Oxytocin Receptors in the Myometrium of the Tammar Wallaby Biol Reprod, October 1, 2002; 67(4): 1242 - 1249. [Abstract] [Full Text] [PDF]

				A. L. Siebel, H. M. Gehring, C. D. Nave, R. A.D. Bathgate, C. E. Borchers, and L. J. Parry Up-Regulation of Mesotocin Receptors in the Tammar Wallaby Myometrium Is Pregnancy-Specific and Independent of Estrogen Biol Reprod, May 1, 2002; 66(5): 1237 - 1243. [Abstract] [Full Text]

				M. E. Miller, S. T. Davidge, and B. F. Mitchell Oxytocin does not directly affect vascular tone in vessels from nonpregnant and pregnant rats Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1223 - H1228. [Abstract] [Full Text] [PDF]

				D. Minjarez, V. Konda, and R. A. Word Regulation of Uterine 5{alpha}-Reductase Type 1 in Mice Biol Reprod, November 1, 2001; 65(5): 1378 - 1382. [Abstract] [Full Text] [PDF]

				B. F. Mitchell and B. Schmid Oxytocin and its Receptor in the Process of Parturition Reproductive Sciences, May 1, 2001; 8(3): 122 - 133. [Abstract] [PDF]

				Y. Zhang, K. G. Stewart, and S. T. Davidge Endogenous estrogen mediates vascular reactivity and distensibility in pregnant rat mesenteric arteries Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H956 - H961. [Abstract] [Full Text] [PDF]

				B.F. Mitchell, X. Fang, and S. Wong Role of Carboxy-Extended Forms of Oxytocin in the Rat Uterus in the Process of Parturition Biol Reprod, December 1, 1998; 59(6): 1321 - 1327. [Abstract] [Full Text]

				W. X. Wu, N. Unno, X. H. Ma, and P. W. Nathanielsz Inhibition of Prostaglandin Production by Nimesulide Is Accompanied by Changes in Expression of the Cassette of Uterine Labor-Related Genes in Pregnant Sheep Endocrinology, July 1, 1998; 139(7): 3096 - 3103. [Abstract] [Full Text] [PDF]

				X. Fang, S. Wong, and B. F. Mitchell Effects of RU486 on Estrogen, Progesterone, Oxytocin, and Their Receptors in the Rat Uterus during Late Gestation Endocrinology, July 1, 1997; 138(7): 2763 - 2768. [Abstract] [Full Text] [PDF]