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

Vodstrcil, Lenka A; Shynlova, Oksana; Westcott, Kerryn T.; Laker, Rhianna C.; Simpson, Emma; Wlodek, Mary E.; Parry, Laura J.

doi:10.1095/biolreprod.110.084301

Cited by 15 publications

(11 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, an attempt to establish its relationship to progesterone in pregnant rat studies indicated that progesterone apparently exerts control over the relaxin [34], and in a human cell line (JAR cells) medroxyprogesterone acetate upregulated relaxin expression [35]. …”

Section: Progesterone and Cervical Functionmentioning

confidence: 99%

Progesterone Interactions with the Cervix: Translational Implications for Term and Preterm Birth

Larsen

Hwang

2011

Infectious Diseases in Obstetrics and Gynecology

View full text Add to dashboard Cite

The uterine cervix plays a vital role in maintaining pregnancy and an equally important role in allowing parturition to occur. Progesterone, either endogenously produced or supplied exogenously, supports the function of the cervix in sustaining intrauterine pregnancy, and the withdrawal of progesterone, either through natural processes or pharmacologic intervention, leads to delivery which underscores the importance of the progesterone's biological activities manifest in normal gestation and pregnancy that ends prematurely. Research crossing many scientific disciplines has demonstrated that progesterone is a pleotropic compound that affects the cervix through cytoplasmic and membrane receptors with profound effects on cellular and molecular functions that influence inflammatory cascades and extracellular matrix, both of which have consequences for parturition. Beyond the local cell and molecular biology of progesterone, it has systemic effects of relevance to pregnancy as well. This paper examines the biology of the cervix from its gross to cellular structure and biological activities of its cell and molecular processes that may be affected by progesterone. The implications of these processes for preterm birth are explored, and direction of current research is in relation to translational medicine implications for diagnostic, prognostic, and therapeutic approaches to threatened preterm birth.

show abstract

Section: Progesterone and Cervical Functionmentioning

confidence: 99%

Progesterone Interactions with the Cervix: Translational Implications for Term and Preterm Birth

Larsen

Hwang

2011

Infectious Diseases in Obstetrics and Gynecology

View full text Add to dashboard Cite

show abstract

“…In my knowledge, there is any others reports about the effect of chlorinated xenobiotics on mRNA expression of this receptor. It is worth to mentioned that high circulating 17β-estradiol is one of the factors which triggers the down-regulation in receptor of RLX during gestation in rats [39]. Hence, it was shown that both studied congeners exerts their estrogenic properties.…”

Section: Results With Discussionmentioning

confidence: 90%

The Preliminary Study About the Involvement of Relaxine in Adverse Effect of Polychlorinated Biphenyls on Bovine Myometrial Contractions

Wróbel¹

2017

J Clin Mol Endocrinol

View full text Add to dashboard Cite

Polychlorinated biphenyls (PCBs) are a group of synthetic xenobiotics, which were used in lots of industrial applications. Two individual congers (PCB 153 and PCB 77) belong to the most prominent environmental contaminations among PCBs, but they have opposite type of configuration and therefore they can exert a different way of action. Since PCBs increased the force of myometrial contractions, in this work, their effect on myometrial sensitivity on inhibitor of myometrial contractions (relaxine, RLX) was studied.Bovine myometrial cells and strips, and luteal cell at 4-8 month of pregnancy, were obtained accidentally in commercial abattoir. They were treated by PCB 153 and PCB 77 and mRNA expression of RLX receptor in myometrial cells and contractions of myometrial strips as well as the secretion of progesterone (P4) and oxytocin (OT) from luteal cells, were measured under their effect.Both studied congeners decreased (P<0.05) the mRNA expression of RLX receptor in myometrium. Admittedly, both PCB 77 and 153 increased (P<0.05) the basal force of contractions, while RLX showed any effect on myometrial contractions. Studied PCBs increased also (P<0.05) secretion of P4 and OT from luteal cells.It is suggested that PCBs can decreased the sensitivity of myometrium on RLX but their direct effect on RLX function have to be further investigated. Keywords: Endocrine Disruption; Pregnancy; Uterus IntroductionPolychlorinated biphenyls (PCBs) are a group of synthetic, chlorinated aryl hydrocarbons, which were extensively used in lots of industrial applications, mainly in transformers, capacitors or as hydraulic fluids, heat exchange liquids as well as plasticizers and others [1]. Because of different degree of chlorination, there are possible up to 209 congeners of PCBs. Among them, 3,3 ' ,4,4 ' -tetrachlorobiphenyl (PCB 77) is one of the most abundant PCB congeners in human milk. This congener is a non-ortho chlorine substituted with coplanar configuration and appear to exert its toxic effects via interacting with the cytosolic aryl hydrocarbon receptor (Ahr). Hence is recognized also as dioxin-like PCBs [2]. Since PCB 77 can affect the cell also through estrogen [3] and glucocorticoid receptors [4], it is recognized as a significant environmental pollutant and endocrine disruptor [3] with a wide spectrum of way of action. Admittedly 2,2',4,4', 5,5'-hexachlorobiphenyl PCB 153 is also one of the most prominent environmental contaminants, but oppositely to PCB 77 is classified as di-ortho, non-coplanar, non-dioxin congener of PCBs [5] and is known to have rather estrogenic properties [6]. Even though PCBs production and use were banned in USA and Europe more than three decades ago, they are still measured in environment [7]. Due to their lipophilic nature and resistance for biodegradation, PCBs have been bio-accumulated in animal tissues [8], also in domestic animals [9,10]. Therefore PCBs have been also measured in food samples [11] and they can be mentioned as a serious health risk.Since PCBs accumulation in preg...

show abstract

“…In other tissues including uterus 25 and cervix 26, estrogen was also reported to upregulate the expression of the relaxin receptors. In this study, modulation of RXFP1 and RXFP2 expression by sex-steroids could provide the basis underlying the effect of these hormones on knee joint laxity.…”

Section: Discussionmentioning

confidence: 99%

“…During late pregnancy in mice, relaxin has no influence on RXFP1 expression 24. Progesterone has been reported to increase the expression of RXFP1 in the pregnant rat uteri 25 while estrogen was found to regulate RXFP1 mRNA expression in human cervix at term 26.…”

Section: Introductionmentioning

confidence: 99%

Sex-Steroid Regulation of Relaxin Receptor Isoforms (RXFP1 & RXFP2) Expression in the Patella Tendon and Lateral Collateral Ligament of Female WKY Rats

Dehghan¹,

Muniandy²,

Yusof³

et al. 2014

Int. J. Med. Sci.

View full text Add to dashboard Cite

The incidence of non-contact knee injury was found higher in female than in male and is related to the phases of the menstrual cycle. This raised the possibility that female sex-steroids are involved in the mechanism underlying this injury via affecting the expression of the receptors for relaxin, a peptide hormone known to modulate ligament laxity. Therefore, this study aims to investigate the effect of sex-steroids on relaxin receptor isoforms (RXFP1 & RXFP2) expression in the ligaments and tendons of the knee. Methods: Ovariectomized adult female WKY rats were treated with different doses of estrogen (0.2, 2, 20 μg/kg), progesterone (4mg) and testosterone (125 & 250μg/kg) for three consecutive days. At the end of the treatment, the animals were sacrificed and the patellar tendon and lateral collateral ligament were harvested for mRNA and protein expression analyses by Real Time PCR and Western blotting respectively. Results: RXFP1, the main isoform expressed in these knee structures and RXFP2 showed a dose-dependent increase in expression with estrogen. Progesterone treatment resulted in an increase while testosterone caused a dose-dependent decrease in the mRNA and protein expression of both relaxin receptor isoforms. Discussion: Progesterone and high dose estrogen up-regulate while testosterone down-regulates RXFP1 and RXFP2 expression in the patellar tendon and lateral collateral ligament of rat's knee. Conclusion: Relaxin receptor isoforms up-regulation by progesterone and high dose estrogen could provide the basis for the reported increase in knee laxity while down-regulation of these receptor isoforms by testosterone could explain low incidence of non-contact knee injury in male.

show abstract

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

Cited by 15 publications

References 32 publications

Progesterone Interactions with the Cervix: Translational Implications for Term and Preterm Birth

Progesterone Interactions with the Cervix: Translational Implications for Term and Preterm Birth

The Preliminary Study About the Involvement of Relaxine in Adverse Effect of Polychlorinated Biphenyls on Bovine Myometrial Contractions

Sex-Steroid Regulation of Relaxin Receptor Isoforms (RXFP1 & RXFP2) Expression in the Patella Tendon and Lateral Collateral Ligament of Female WKY Rats

Contact Info

Product

Resources

About