Relaxin Receptor LGR7 (RXFP1) Is Regulated by Estrogen

Maseelall, Priya; Gardner, Jeff; Wojtczuk, Andrea; Weiss, Gerson; Goldsmith, Laura T.

doi:10.1111/j.1749-6632.2009.04048.x

Cited by 8 publications

(9 citation statements)

References 6 publications

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“…Actions of relaxin are mediated via its receptor, RXFP1, a transmembrane protein belonging to the leucine-rich G protein receptor family (Hsu et al 2002). Results of the present study, indicating that exposure of gilts to EV for 2 weeks from birth increased uterine RXFP1 expression at PND 14, support previous studies that showed estrogens increased porcine uterine relaxin binding (Mercado-Simmen et al 1982) as well as RXFP1 gene expression in the porcine reproductive tract (Yan et al 2008) and in a human uterine fibroblast cell line (Maseelall et al 2009). Importantly, data also show that the estrogen-induced increase in uterine RXFP1 expression observed on PND 14 is similar to that observed in adult endometrium obtained from neonatally EV-exposed gilts on PxD 12.…”

Section: Discussionsupporting

confidence: 81%

Transient estrogen exposure from birth affects uterine expression of developmental markers in neonatal gilts with lasting consequences in pregnant adults

Chen¹,

Wiley²,

Ho³

et al. 2010

Reproduction

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Disruption of estrogen-sensitive, estrogen receptor (ER)-dependent events during porcine uterine development between birth (postnatal dayZPND 0) and PND 14 affects patterns of uterine morphoregulatory gene expression in the neonate with lasting consequences for reproductive success. Uterine capacity for conceptus support is reduced in pregnant adult gilts exposed to estradiol valerate (EV) for 14 days from birth. Objectives here were to determine effects of EV exposure from birth through PND 13 on neonatal uterine and adult endometrial markers of growth, patterning, and remodeling. Targets included the relaxin receptor (RXFP1), estrogen receptor-a (ESR1) and vascular endothelial growth factor (VEGFA), morphoregulatory markers HOXA10 and WNT7A, and the matrix metalloproteinases (MMP)2 and MMP9. Gilts were treated daily with EV (50 mg/kg body weight per day, i.m.) or corn oil vehicle from birth through PND 13. Uteri were obtained from neonates on PND 14 and from adults on pregnancy day 12 (PxD 12). In neonates, EV exposure from birth increased uterine RXFP1 gene expression, and both ESR1 and VEGFA proteins. At PxD 12, endometrial RXFP1 mRNA remained elevated, while ESR1 protein was reduced. Early EV treatment decreased neonatal uterine WNT7A, but increased HOXA10 expression. WNT7A expression was reduced in EV-treated adults. Transient EV exposure increased MMP9 transcripts at PND 14, whereas both latent and active MMP9 activity was increased due to early EV treatment in adults on PxD 12. Results support the hypothesis that transient, estrogen-induced disruption of porcine uterine development from birth alters early programming events that lead to functional consequences in the adult.

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Section: Discussionsupporting

confidence: 81%

Transient estrogen exposure from birth affects uterine expression of developmental markers in neonatal gilts with lasting consequences in pregnant adults

Chen¹,

Wiley²,

Ho³

et al. 2010

Reproduction

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“…In addition, Rxfp1 gene expression increased after estradiol valerate treatment from birth in the uterus of Postpartum Day 2 pigs, again indicating the positive effects of 17b-estradiol on Rxfp1 [13]. Treatment of human lower uterine segment fibroblasts in vitro with estrogen also increases Rxfp1 mRNA expression [31]. This contradicts the data in the present study, because RU486 treatment increased 17b-estradiol and Esr1 but resulted in a decrease in RXFP1.…”

Section: Regulation Of Myometrial Rxfp1contrasting

confidence: 67%

Progesterone Withdrawal, and Not Increased Circulating Relaxin, Mediates the Decrease in Myometrial Relaxin Receptor (RXFP1) Expression in Late Gestation in Rats1

Vodstrcil¹,

Shynlova²,

Westcott³

et al. 2010

Biology of Reproduction

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In pregnant rats, a significant decrease in myometrial relaxin family peptide receptor 1 (RXFP1) expression, indicative of a functional relaxin withdrawal for activation of myometrial contractions, occurs in late gestation and during spontaneous labor. This coincides with the highest level of circulating relaxin and a decrease in progesterone. We investigated the potential regulatory role of these two systemic factors on myometrial RXFP1 expression by examining the effects of the antiprogestin RU486 and a monoclonal antibody against rat relaxin (MCA1) in pregnant rats. Rats were injected with RU486 on Gestational Day (GD) 7, 16, or 19 and were killed on GD 8, 17, or 20. RU486 caused a significant reduction in myometrial RXFP1. Plasma progesterone and 17beta-estradiol levels were increased in RU486-treated animals compared with controls. RU486 treatment also caused significant increases in myometrial Esr1 and Vegf and a decrease in Esr2. MCA1 was administered i.v. to rats from GD 17 to GD 19. On GD 20, no significant effect of MCA1 treatment on myometrial RXFP1 expression was observed compared with controls. Furthermore, there was no change in Esr1 or Esr2. A significant reduction in myometrial Vegf, however, was observed. We suggest that blocking progesterone action with RU486 increases plasma 17beta-estradiol and myometrial Esr1 and results in decreased RXFP1 expression. In summary, myometrial RXFP1 expression is mediated mainly by progesterone and not circulating relaxin in pregnant rats.

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“…Relaxin binds to the 2002 discovered relaxin receptor 1 (LGR7) and with lower affinity to the closely related relaxin receptor 2 (LGR8), which are G proteincoupled transmembrane proteins with a characteristic leucinerich repeat extracellular domain [10]. Although LGR7 has recently been described in human cervical fibroblasts, its impact on human parturition remains unclear [11].…”

Section: Introductionmentioning

confidence: 99%

Relaxin and gonadal steroid receptors in uterosacral ligaments of women with and without pelvic organ prolapse

et al. 2011

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Relaxin Receptor LGR7 (RXFP1) Is Regulated by Estrogen

Cited by 8 publications

References 6 publications

Transient estrogen exposure from birth affects uterine expression of developmental markers in neonatal gilts with lasting consequences in pregnant adults

Transient estrogen exposure from birth affects uterine expression of developmental markers in neonatal gilts with lasting consequences in pregnant adults

Progesterone Withdrawal, and Not Increased Circulating Relaxin, Mediates the Decrease in Myometrial Relaxin Receptor (RXFP1) Expression in Late Gestation in Rats1

Relaxin and gonadal steroid receptors in uterosacral ligaments of women with and without pelvic organ prolapse

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