Oxytocin receptor gene expression in rat uterus: regulation by ovarian steroids.

The present study was designed to investigate a possible role for ovarian steroids in the regulation of rat uterine oxytocin receptor (OTR) mRNA expression before labour. By using a competitive RT-PCR system, we have previously reported that parturition was associated with high levels of uterine OTR mRNA in all the animals examined. On the other hand, near term, some rats showed high OTR mRNA levels while others did not. We therefore examined the changes in OTR mRNA expression before and during prostaglandin F(2)(alpha) (PGF(2)(alpha))-induced parturition; a paradigm adopted to reduce the variation in the onset of parturition. Injection of PGF(2)(alpha) on day 18 of pregnancy significantly increased OTR mRNA expression in all the rats within 24 h of treatment, suggesting that the variation in OTR mRNA levels during spontaneous parturition may be due to the difference in the timing of the onset of parturition. The increase in OTR mRNA was significantly abolished by injection of the anti-oestrogen compound, tamoxifen. The stimulatory action of oestrogen on OTR mRNA expression was then examined in the presence or absence of ovarian factors. Pregnant rats were ovariectomized (OVX) or sham-operated on day 18 of pregnancy and either oestrogen or vehicle was administered 6 h after the surgical operation. Oestrogen increased OTR mRNA significantly in OVX rats 18 h after administration compared with sham-operated animals. Moreover, ovariectomy alone on day 18 of pregnancy increased OTR mRNA expression to a level which reached statistical significance 24 h after the operation. In addition, oestrogen treatment increased OTR mRNA levels in OVX virgin rats in which progesterone tubes were implanted for 1 week and removed 6 h before oestrogen injection. The stimulatory effect of oestrogen was not observed in rats in which the progesterone tubes were implanted for 1 week and not removed. These results suggest that the decline of progesterone is necessary for the expression of the stimulatory effects of oestrogen on uterine OTR mRNA.

[1]  S. Lye,et al.  Increased expression of the rat myometrial oxytocin receptor messenger ribonucleic acid during labor requires both mechanical and hormonal signals. , 1998, Biology of reproduction.

[2]  Hans H. Zingg,et al.  Inhibition of oxytocin receptor function by direct binding of progesterone , 1998, Nature.

[3]  S. Narumiya,et al.  Failure of parturition in mice lacking the prostaglandin F receptor. , 1997, Science.

[4]  B. Mitchell,et al.  Effects of RU486 on estrogen, progesterone, oxytocin, and their receptors in the rat uterus during late gestation. , 1997, Endocrinology.

[5]  K. Stevenson,et al.  Regulation of oxytocin, oestradiol and progesterone receptor concentrations in different uterine regions by oestradiol, progesterone and oxytocin in ovariectomized ewes. , 1996, The Journal of endocrinology.

[6]  Xiao Hong Ma,et al.  Regulation of the estrogen receptor and its messenger ribonucleic acid in the ovariectomized sheep myometrium and endometrium: the role of estradiol and progesterone. , 1996, Biology of reproduction.

[7]  T. Higuchi,et al.  Changes in oxytocin receptor mRNA in the rat uterus measured by competitive reverse transcription-polymerase chain reaction. , 1996, The Journal of endocrinology.

[8]  Y. Kitamura,et al.  Expression of oxytocin receptor in human pregnant myometrium. , 1996, Endocrinology.

[9]  P. Nathanielsz,et al.  Characterization of oxytocin receptor expression and distribution in the pregnant sheep uterus. , 1996, Endocrinology.

[10]  C. Breton,et al.  Oxytocin receptor gene expression in the rat uterus during pregnancy and the estrous cycle and in response to gonadal steroid treatment. , 1995, Endocrinology.

[11]  D. Banville,et al.  Structure, characterization, and expression of the rat oxytocin receptor gene. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[12]  S. Nomura,et al.  Expression and localization of human oxytocin receptor mRNA and its protein in chorion and decidua during parturition. , 1994, The Journal of clinical investigation.

[13]  V. Mahesh,et al.  Regulation of estrogen receptor protein and messenger ribonucleic acid by estradiol and progesterone in rat uterus , 1993, The Journal of Steroid Biochemistry and Molecular Biology.

[14]  R. Fairclough,et al.  Role of progesterone in the control of endometrial oxytocin receptors at luteolysis in sheep. , 1993, Journal of reproduction and fertility.

[15]  R. Fairclough,et al.  Increase in concentration of uterine oxytocin receptors and decrease in response to 13,14-dihydro-15-keto prostaglandin F2 alpha in ewes after withdrawal of exogenous progesterone. , 1992, Journal of reproduction and fertility.

[16]  J. Hixon,et al.  Role of progesterone and oestradiol in the regulation of uterine oxytocin receptors in ewes. , 1992, Journal of reproduction and fertility.

[17]  A. Peri,et al.  Oxytocin and V1 vasopressin receptors in rabbit endometrium during pregnancy. , 1991, Journal of reproduction and fertility.

[18]  G. Lamming,et al.  Control of endometrial oxytocin receptor and uterine response to oxytocin by progesterone and oestradiol in the ewe. , 1990, Journal of reproduction and fertility.

[19]  M. Serio,et al.  Vasopressin and oxytocin receptors in vagina, myometrium, and oviduct of rabbits. , 1988, Endocrinology.

[20]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[21]  W. W. Leavitt,et al.  Progestin-induced down regulation of nuclear estrogen receptor in uterine decidual cells: analysis of receptor synthesis and turnover by the density-shift method. , 1986, Biochemical and biophysical research communications.

[22]  W. Okulicz,et al.  Rapid recovery of nuclear estrogen receptor and oxytocin receptor in the ovine uterus following progesterone withdrawal. , 1985, Journal of steroid biochemistry.

[23]  P. Husslein,et al.  Oxytocin receptors in the human uterus during pregnancy and parturition. , 1984, American journal of obstetrics and gynecology.

[24]  R. Bridges.  A quantitative analysis of the roles of dosage, sequence, and duration of estradiol and progesterone exposure in the regulation of maternal behavior in the rat. , 1984, Endocrinology.

[25]  M. Soloff,et al.  Correlation between oxytocin receptor concentration and responsiveness to oxytocin in pregnant rat myometrium: effects of ovarian steroids. , 1983, Endocrinology.

[26]  M. Soloff,et al.  Regulation of oxytocin receptor concentration in rat uterine explants by estrogen and progesterone. , 1983, Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire.

[27]  M. Soloff,et al.  Oxytocin receptors: triggers for parturition and lactation? , 1979, Science.

[28]  A. Hsueh,et al.  Control of uterine estrogen receptor levels by progesterone. , 1976, Endocrinology.

[29]  M. Soloff.  Uterine receptor for oxytocin: effects of estrogen. , 1975, Biochemical and biophysical research communications.

[30]  J. Amico,et al.  The duration of estradiol and progesterone exposure prior to progesterone withdrawal regulates oxytocin mRNA levels in the paraventricular nucleus of the rat. , 1997, Endocrine research.

[31]  G. Jenkin,et al.  Oxytocin receptor development in ovine uterus and cervix throughout pregnancy and at parturition as determined by in situ hybridization analysis. , 1996, Journal of reproduction and fertility.

[32]  T. Insel,et al.  Increased accumulation of oxytocin messenger ribonucleic acid in the hypothalamus of the female rat: induction by long term estradiol and progesterone administration and subsequent progesterone withdrawal. , 1995, Endocrinology.

[33]  T. Higuchi.  Oxytocin: a neurohormone, neuroregulator, paracrine substance. , 1995, The Japanese journal of physiology.

[34]  V. Mahesh,et al.  Changes in rat uterine estrogen receptor messenger ribonucleic acid levels during estrogen- and progesterone-induced estrogen receptor depletion and subsequent replenishment. , 1993, Biology of reproduction.

[35]  R. Brenner,et al.  Uterine estrogen receptors are increased by RU486 in late pregnant rhesus macaques but not after spontaneous labor. , 1990, The Journal of clinical endocrinology and metabolism.

[36]  D. Dorsa,et al.  Printed in U.S.A. Copyright © 1997 by The Endocrine Society Cloning, Novel Promoter Sequence, and Estrogen Regulation of a Rat Oxytocin Receptor Gene* , 2022 .