Relaxin Receptor in the Rat Myometrium: Regulation by Estrogen and Relaxin*

Mercado-Simmen, Rosalia C.; Bryant‐Greenwood, Gillian D.; Greenwood, F. C.

doi:10.1210/endo-110-1-220

Cited by 98 publications

(61 citation statements)

References 29 publications

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“…Moreover, while uterine RXFP1 expression was documented in tissues obtained at birth (Yan et al 2006b), similar data for neonatal porcine cervical tissues are lacking. The fact that E administered from birth increased RXFP1 expression in both the uterus and cervix on PND 2 supports and extends previous studies indicating the importance of estrogen in sensitizing reproductive tissues to RLX (Mercado-Simmen et al 1982, Downing & Hollingsworth 1992, 1993. Results are consistent with the idea that estrogen priming can facilitate (Vasilenko et al 1980, Vasilenko & Mead 1987 or enhance responsiveness of RLX target tissues (Adams et al 1989).…”

Section: Effects Of Relaxin On Neonatal Uterus and Cervixsupporting

confidence: 87%

Relaxin (RLX) and estrogen affect estrogen receptor α, vascular endothelial growth factor, and RLX receptor expression in the neonatal porcine uterus and cervix

Yan¹,

Chen²,

Wiley³

et al. 2008

Reproduction

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The porcine female reproductive tract undergoes estrogen receptor (ER) a-dependent development after birth (postnatal dayZPND 0), the course of which can determine adult uterine function. Uterotrophic effects of relaxin (RLX) in the porcine neonate are age specific and may involve ER activation. Here, objectives were to determine effects of RLX and estrogen administered from birth on uterine and cervical growth and expression of ERa, vascular endothelial growth factor (VEGF), and the RLX receptor (RXFP1). On PND 0, gilts were treated with the antiestrogen ICI 182 780 (ICI) or vehicle alone and, 2 h later, were given estradiol-17b (E) or porcine RLX for 2 days. Neither RLX nor E affected uterine wet weight or protein content on PND 2. However, RLX, but not E, increased cervical wet weight and protein content when compared with controls. Pretreatment with ICI did not inhibit RLX-stimulated cervical growth. Uterine and cervical ERa increased in response to RLX, but not E. Both RLX and E increased VEGF in the uterus and cervix on PND 2. Pretreatment with ICI increased VEGF in both tissues and increased RLX-induced cervical VEGF. In the uterus E, but not RLX, increased RXFP1 mRNA. In the cervix, E increased RXFP1 gene expression whereas RLX decreased it. Results indicate that the neonatal uterus and cervix are sensitive to E and RLX and that growth responses to RLX in these tissues differ by PND 2. Effects of RLX on uterine and cervical ERa and VEGF expression may be important for neonatal reproductive tract development. Reproduction (2008) 135 705-712

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Section: Effects Of Relaxin On Neonatal Uterus and Cervixsupporting

confidence: 87%

Relaxin (RLX) and estrogen affect estrogen receptor α, vascular endothelial growth factor, and RLX receptor expression in the neonatal porcine uterus and cervix

Yan¹,

Chen²,

Wiley³

et al. 2008

Reproduction

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“…It is transformed from a quiescent organ during the first part of gestation to a highly contractile organ at term. Sex steroids exert an overall regulation of myometrial activity and it is generally accepted that estrogen promotes uterine activity (Mercado Simmen et al 1982) whereas progesterone favors uterine quiescence (Csapo 1956, Lye & Porter 1978. The regulation of uterine activity by sex steroids includes prostaglandin production (Engstrøm 2001), prostaglandin F 2 receptor function (Engstrøm et al 2000) and oxytocin receptors (Engstrøm et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Desensitization of beta2-adrenoceptor function in non-pregnant rat myometrium is modulated by sex steroids

Engstrøm

Vilhardt²,

Bratholm³

et al. 2001

Journal of Endocrinology

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The effects of in vivo treatment with estrogen and progesterone on isoproterenol-induced uterine relaxation and 2 -adrenoceptor ( 2 AR) mRNA production in nonpregnant rat myometrium were investigated. Whether homologous myometrial desensitization of 2 AR function was dependent on or modulated by the two steroids was also examined.Estrogen treatment alone or in combination with progesterone reduced maximal relaxation (E max ) of isolated uterine strips subsequently challenged with isoproterenol whereas progesterone alone had no effect on this parameter. The reduction was accompanied by an enhanced 2 AR mRNA concentration. The concentration of isoproterenol giving half-maximal relaxing response (EC 50 ) increased following estrogen treatment and this effect was curbed by progesterone.Isoproterenol had no effect on 2 AR transcription irrespective of the steroid regimes employed. E max of isolated uterine strips was reduced following prolonged in vivo treatment with isoproterenol but the effect was found only when estrogen alone was administered concomitantly. Finally, in vivo treatment with isoproterenol increased EC 50 of uterine strips subsequently stimulated with isoproterenol in vitro. This effect was independent of steroid treatment.We conclude that homologous desensitization of 2 AR function in non-pregnant rat myometrium in terms of sensitivity (EC 50 ) is independent of sex steroids but in terms of maximal response (E max ) occurs only in the presence of estrogen. We speculate whether progesterone withdrawal in connection with the well-known estrogen dominance at rat parturition may strengthen the desensitization induced by 2 AR activation and thus contribute to the transformation of the uterus from a quiescent to a highly contractile organ.

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“…Development of a receptor binding assay to characterize these receptors has been di cult. Using a [ 125 I]-labelled porcine relaxin prepared with the modi®ed method of Bolton & Hunter (1973), receptors for relaxin were studied in the homogenate preparations of rat myometrium (Mercado-Simmen et al, 1980;1982a), mouse uterus and porcine myometrium and cervix (Mercado-Simmen et al, 1982b). Incubation of tissue homogenates with radiolabelled relaxin followed by centrifugation to separate bound and free ligand shows high levels of non-speci®c binding Garibay-Tupas et al, 1995) because relaxin binds to many materials (Greenwood et al, 1981).…”

Section: Introductionmentioning

confidence: 99%

Quantitative autoradiographic studies of relaxin binding in rat atria, uterus and cerebral cortex: characterization and effects of oestrogen treatment

Tan

Wade

Tregear

et al. 1999

British J Pharmacology

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1 The binding characteristics of the relaxin receptor in rat atria, uterus and cortex were studied using a [ 33 P]-labelled human gene 2 relaxin (B33) and quantitative receptor autoradiography. 2 The binding kinetics of [ 33 P]-human gene 2 relaxin (B33) were investigated in slide-mounted rat atrial sections. The binding achieved equilibrium after 60 min incubation at room temperature (23+18C) and dissociated slowly. The association and dissociation rate constants were 4.31+0.34610 8 M 71 min 71 and 1.55+0.38610 73 min 71 respectively. Thus, the kinetic dissociation constant was 3.46+0.59 pM. 3 Binding was saturable to a single population of non-interacting sites throughout atria, in uterine myometrium and the 5th layer of cerebral cortex. The binding a nities (pK D ) of [ 33 P]-human gene 2 relaxin (B33) were 8.92+0.09 in atrial myocardium and 8.79+0.04 in cerebral cortex of male rats, and 8.79+0.10 in uterine myometrium. Receptor densities in the cerebral cortex and atria were higher than in uterine myometrium, indicating that relaxin also has important roles in nonreproductive tissues. 4 In male rats, treatment with 17b-oestradiol (20 mg in 0.1 ml sesame oil s.c., 18 ± 24 h) signi®cantly decreased the density of relaxin receptors in atria and cerebral cortex. Identical treatment in female rats had no signi®cant e ect in atria and cerebral cortex, but it signi®cantly increased the density of relaxin receptors in uterine myometrium. 5 Relaxin binding was competitively displaced by porcine and rat native relaxins. Porcine native relaxin binds to the relaxin receptor in male rat atria (8.90+0.02), and cerebral cortex (8.90+0.03) and uterine myometrium (8.89+0.03) with a nities not signi®cantly di erent from human gene 2 (B33) relaxin. Nevertheless, rat relaxin binds to the receptors with a nities (8.35+0.09 in atria, 8.22+0.07 in cerebral cortex and 8.48+0.06 in uterine myometrium) signi®cantly less than human gene 2 (B33) and porcine relaxins. 6 Quantitative receptor autoradiography is the method of choice for measurement of a nities and densities of relaxin receptor in atria, uterine myometrium and cerebral cortex. High densities were found in all these tissues. 17b-Oestradiol treatment produced complex e ects where it increased the densities of relaxin receptors in uterus but decreased those in atria and cerebral cortex of the male rats, and had no e ect on the atria and cerebral cortex of the female rats.

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Relaxin Receptor in the Rat Myometrium: Regulation by Estrogen and Relaxin*

Cited by 98 publications

References 29 publications

Relaxin (RLX) and estrogen affect estrogen receptor α, vascular endothelial growth factor, and RLX receptor expression in the neonatal porcine uterus and cervix

Relaxin (RLX) and estrogen affect estrogen receptor α, vascular endothelial growth factor, and RLX receptor expression in the neonatal porcine uterus and cervix

Desensitization of beta2-adrenoceptor function in non-pregnant rat myometrium is modulated by sex steroids

Quantitative autoradiographic studies of relaxin binding in rat atria, uterus and cerebral cortex: characterization and effects of oestrogen treatment

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