Action of relaxin on uterine contractions - a review

Downing, Sandra J.; Hollingsworth, Michael A.

doi:10.1530/jrf.0.0990275

Cited by 38 publications

(18 citation statements)

References 13 publications

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“…However, it also requires the withdrawal of mechanisms that maintain uterine quiescence, including inhibitors of CAPs. The ovarian peptide hormone relaxin is thought to act as an inhibitor of spontaneous myometrial contractions during pregnancy [3,4]. In vitro studies show that porcine relaxin inhibits contractile activity in the nonpregnant (NP) and pregnant rat until midpregnancy, but that the myometrium is completely refractory to the inhibitory effect of relaxin by Gestational Day (GD) 19 [5,6].…”

Section: Introductionmentioning

confidence: 99%

Decreased Expression of the Rat Myometrial Relaxin Receptor (RXFP1) in Late Pregnancy Is Partially Mediated by the Presence of the Conceptus1

Vodstrcil

Shynlova

Verlander

et al. 2010

Biology of Reproduction

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The actions of relaxin are mediated by relaxin family peptide receptor 1 (Rxfp1). In pregnant mice, myometrial Rxfp1 expression decreases at term, coinciding with the highest level of circulating relaxin. This down-regulation in Rxfp1 in reproductive tissues has not been investigated in other pregnant animals, nor are the regulatory mechanisms known. In the present study, we examined Rxfp1 gene and protein expression in the nonpregnant, pregnant, and postpartum rat uterus. The potential effects of local conceptus-derived factors on Rxfp1 expression were then examined in unilaterally pregnant rats. Immunoreactive RXFP1 was predominantly detected in the circular smooth muscle layer in the myometrium and in the decidualized endometrium. Rxfp1 was expressed in the rat myometrium from early to midgestation at levels similar to those in nonpregnant rat myometrium, with a significant reduction in expression at both the transcriptional and translational levels during late gestation. In unilaterally pregnant rats, myometrial Rxfp1 was higher in the nongravid compared to the gravid uterine horn, demonstrating a local negative influence of the fetal-placental unit on Rxfp1 expression. In summary, the down-regulation in myometrial Rxfp1 expression at the end of gestation in the rat is partially mediated by the fetal-placental unit and is indicative of a functional withdrawal of relaxin. This may represent a novel mechanism for the activation of spontaneous uterine contractions at labor in this species.

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Section: Introductionmentioning

confidence: 99%

Decreased Expression of the Rat Myometrial Relaxin Receptor (RXFP1) in Late Pregnancy Is Partially Mediated by the Presence of the Conceptus1

Vodstrcil

Shynlova

Verlander

et al. 2010

Biology of Reproduction

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“…Relaxin is one of the most potent known relaxants of uterine smooth muscle (Downing & Hollingsworth, 1993). It is a polypeptide hormone mainly derived from the corpus luteum and has a role in maintaining quiescence of the uterus during pregnancy.…”

Section: Introductionmentioning

confidence: 99%

“…The two mechanisms which have been proposed to explain the inhibitory action of relaxin in the uterus are located at different sites in the cell. There is evidence that relaxin may act via a cell surface receptor to activate the adenylyl cyclase pathway and stimulate an adenosine 3': 5'-cyclic monophosphate (cyclic AMP)-dependent protein kinase which in turn modulates intracellular enzymes and proteins (Sanborn & Anwer, 1990;Downing & Hollingsworth, 1993). Relaxin has been shown to increase the uterine concentration of cyclic AMP (Cheah & Sherwood, 1980;Judson et al, 1980;Sanborn et al, 1980;Hsu et al, 1985;Osa et al, 1991) and to increase 'Author for correspondence.…”

Section: Introductionmentioning

confidence: 99%

Cellular localization of the inhibitory action of relaxin against uterine spasm

Hughes

Hollingsworth

1995

British J Pharmacology

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1 The aim of this study was to determine whether the site of action of relaxin as a relaxant of rat myometrium is at the cell membrane or at an intracellular site. Therefore, the potency of relaxin was determined against spasms reliant predominantly upon either extracellular Ca2+ or intracellular Ca2". Uterine spasms dependent upon extracellular Ca2" were elicited by (i) oxytocin (0.2 nM) (ii) Bay K 8644(1 yM) in 10 mm K+-rich PSS and (iii) KCl (80 mM). Uterine spasm dependent upon intracellular Ca2+ was elicited by oxytocin (20 nM) in the presence of nifedipine (500 nM). The effects of relaxin against these spasmogens were compared with those of levcromakalim, nifedipine and salbutamol. 2 Relaxin (0.2-6.3 nM), levcromakalim (25-800 nM), salbutamol (1-63 nM) and nifedipine (1-250 nM) caused concentration-dependent inhibition of the spasm evoked by oxytocin (0.2 nM) and relaxin was the most potent relaxant. 3 Relaxin and nifedipine were slightly less potent against the spasm induced by Bay K 8644 (1 uM) than against spasm induced by oxytocin (0.2 nM) (15 fold and 13 fold respectively). Levcromakalim and salbutamol were equipotent against the spasm evoked by Bay K 8644 (1 uM) and that evoked by oxytocin (0.2 nM). 4 Relaxin induced only 47 + 7% inhibition of the KCl (80 mM)-evoked spasm at a concentration of 0.8 JM. Levcromakalim was much less potent (427 fold) against the spasm evoked by KCl (80 mM) than against the spasm evoked by oxytocin (0.2 nM). The potency of salbutamol against the spasm evoked by KCl (80 mM) was modestly reduced (14 fold) compared to that against the spasm evoked by oxytocin (0.2 nM). The potency of nifedipine against the KCl (80 mM)-evoked spasm was not different from that against the oxytocin (0.2 nM)-evoked spasm. 5 The potencies of relaxin and levcromakalim against the spasm evoked by oxytocin (20 nM) + nifedipine (500 nM) were greatly reduced (74 fold and 234 fold respectively) compared to their potencies against the spasm evoked by oxytocin (0.2 nM). The potency of salbutamol against these two spasmogens was not different. 6 Relaxin was much less potent against the spasm dependent upon intracellular Ca21 (that induced by oxytocin (20 nM) + nifedipine (500 nM)) than against the spasms dependent upon extracellular Ca2 , those induced by oxytocin (0.2 nM) and Bay K 8644 (1 gM). In this regard, relaxin resembled levcromakalim and nifedipine rather than salbutamol. Therefore, the major site of action of relaxin appears to be located at the plasma membrane rather than at an intracellular level. The observation that relaxin was less effective against the KCl (80 mM)-induced spasm than against the oxytocin (0.2 nM)-evoked spasm may indicate that relaxin has a minor action involving K + -channel opening. 7 High concentrations of relaxin (up to 1 gM) induced significant inhibition of the spasm dependent upon intracellular Ca2+. Thus at high concentrations relaxin also appears to have an additional intracellular action.

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“…The peptide hormone relaxin is thought to inhibit spontaneous myometrial contractions during pregnancy and prevent the premature activation of contractile-associated proteins (CAPs), such as oxytocin [1][2][3]. Relaxin treatment abolishes the plateau component of the action potential, characteristic of the electrical activity of the circular myometrium, thus reducing the contractile response [4].…”

Section: Introductionmentioning

confidence: 99%

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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Action of relaxin on uterine contractions - a review

Cited by 38 publications

References 13 publications

Decreased Expression of the Rat Myometrial Relaxin Receptor (RXFP1) in Late Pregnancy Is Partially Mediated by the Presence of the Conceptus1

Decreased Expression of the Rat Myometrial Relaxin Receptor (RXFP1) in Late Pregnancy Is Partially Mediated by the Presence of the Conceptus1

Cellular localization of the inhibitory action of relaxin against uterine spasm

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

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