Increased Expression of the Relaxin Receptor (LGR7) in Human Endometrium during the Secretory Phase of the Menstrual Cycle

Bond, Courtney Peta; Parry, Laura J.; Samuel, Chrishan S.; Gehring, Helen M.; Lederman, Fiona; Rogers, Peter A. W.; Summers, Roger J.

doi:10.1196/annals.1282.020

Cited by 19 publications

(21 citation statements)

References 30 publications

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“…Dysregulation of microRNAs or differential methylation of RXFP1 may be at play here. External signals, perhaps hormonal, may regulate expression of RXFP1 (31,32). RXFP1 expression in IPF in our dataset did not differ by sex, however, suggesting that the loss of RXFP1 in fibrosis is independent of sex.…”

Section: Discussionmentioning

confidence: 56%

Expression of RXFP1 Is Decreased in Idiopathic Pulmonary Fibrosis. Implications for Relaxin-based Therapies

Tan

Tedrow

Dutta

et al. 2016

Am J Respir Crit Care Med

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Rationale: Relaxin is a hormone that has been considered as a potential therapy for patients with fibrotic diseases.Objectives: To gauge the potential efficacy of relaxin-based therapies in idiopathic pulmonary fibrosis (IPF), we studied gene expression for relaxin/insulin-like family peptide receptor 1 (RXFP1) in IPF lungs and controls.Methods: We analyzed gene expression data obtained from the Lung Tissue Research Consortium and correlated RXFP1 gene expression data with cross-sectional clinical and demographic data. We also employed ex vivo donor and IPF lung fibroblasts to test RXFP1 expression in vitro. We tested CGEN25009, a relaxin-like peptide, in lung fibroblasts and in bleomycin injury. Measurements and Main Results:We found that RXFP1 is significantly decreased in IPF. In patients with IPF, the magnitude of RXFP1 gene expression correlated directly with diffusing capacity of the lung for carbon monoxide (P , 0.0001). Significantly less RXFP1 was detected in vitro in IPF fibroblasts than in donor controls. Transforming growth factor-b decreased RXFP1 in both donor and IPF lung fibroblasts. CGEN25009 was effective at decreasing bleomycin-induced, acid-soluble collagen deposition in vivo. The relaxin-like actions of CGEN25009 were abrogated by RXFP1 silencing in vitro, and, in comparison with donor lung fibroblasts, IPF lung fibroblasts exhibited decreased sensitivity to the relaxin-like effects of CGEN25009.Conclusions: IPF is characterized by the loss of RXFP1 expression. RXFP1 expression is directly associated with pulmonary function in patients with IPF. The relaxin-like effects of CGEN25009 in vitro are dependent on expression of RXFP1. Our data suggest that patients with IPF with the highest RXFP1 expression would be predicted to be most sensitive to relaxin-based therapies.Keywords: relaxin; pulmonary fibrosis; transforming growth factor-b; RXFP1 At a Glance CommentaryScientific Knowledge on the Subject: Relaxin and relaxinbased therapies have been considered as potential therapies for pulmonary fibrosis.What This Study Adds to the Field: We found that expression of the relaxin receptor, RXFP1, is decreased in idiopathic pulmonary fibrosis and is associated with impaired pulmonary function. Understanding how RXFP1 is regulated is critical to the success of relaxin-based therapies in idiopathic pulmonary fibrosis.

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Section: Discussionmentioning

confidence: 56%

Expression of RXFP1 Is Decreased in Idiopathic Pulmonary Fibrosis. Implications for Relaxin-based Therapies

Tan

Tedrow

Dutta

et al. 2016

Am J Respir Crit Care Med

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“…However relaxin is clearly not mandatory during the induction or maintenance of pregnancy, because women without ovaries can become pregnant by ovum donation even though they have undetectable levels of circulating relaxin (Johnson et al, 1991). Relaxin secretion also correlates with increased expression of RXFP1 mRNA and relaxin binding in the human endometrium in the secretory phase of the menstrual cycle (Bond et al, 2004;Campitiello et al, 2011).…”

Section: Physiologic Roles Of Relaxin Family Peptide Receptors Andmentioning

confidence: 89%

International Union of Basic and Clinical Pharmacology. XCV. Recent Advances in the Understanding of the Pharmacology and Biological Roles of Relaxin Family Peptide Receptors 1–4, the Receptors for Relaxin Family Peptides

Halls¹,

Bathgate²,

Sutton³

et al. 2015

Pharmacol Rev

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117

118

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“…Third, RXFP1 mRNA was translated into the protein in the testis during development, and the protein encoded by RXFP1 was localised in the same cell types by which RXFP1 transcripts were expressed. The antiserum used in this study was generated against recombinant MBP-RXFP1 endodomain, and its specificity was validated by demonstrating the recognition of RXFP1 endodomain, but not RXFP2 endodomain, on western blotting, and by indicating the immunolocalisation in uterine endometrium and myometrium where RLN receptor is expressed in humans, rodents and pigs (Mercado-Simmen et al 1982, Weiss & BryantGreenwood 1982, Kohsaka et al 1998, Bond et al 2004. The expression of RLF/INSL3 receptor RXFP2 is also observed in the testis of humans (Anand- Ivell et al 2006) and rodents (Feng et al 2007), but it is clear that our generated antiserum does not detect the RXFP2 since it did not cross react with recombinant RXFP2 as mentioned above.…”

Section: Discussionmentioning

confidence: 99%

Evidence for expression of relaxin hormone-receptor system in the boar testis

Kato¹,

Siqin²,

Minagawa³

et al. 2010

Journal of Endocrinology

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Although the physiological role of relaxin (RLN) in males remains largely unknown, there is limited evidence that the testis might be a candidate source and target of RLN in boars, as RLN transcripts are detected in the boar testis and it contains RLN-binding sites. To determine whether the boar testis acts as a source and target tissue of RLN, we characterised the expression pattern and cellular localisation of both RLN and its own receptor LGR7 (RXFP1) in boar testes during postnatal development by molecular and immunological approaches. Testes were collected from Duroc boars, and partial cDNA sequences of the boar homologue of human RXFP1 were identified. RLN expression increased through puberty onwards, while RXFP1 expression changed little during development.RLN mRNA and protein expression were restricted to the Leydig cells, whereas both Leydig cells and seminiferous epithelial cells expressed RXFP1 mRNA and protein.Interestingly, RLN was expressed in the testis as an 18 kDa form (the expected size of proRLN), but not as the 6 kDa mature form, during development because of a lack of the enzyme required for proRLN processing. In contrast, RXFP1 was detected at all stages as specific bands of 75 and 91-95 kDa (likely non-glycosylated and glycosylated RXFP1 respectively). Thus, we provide evidence for expression of RLN-RXFP1 ligand-receptor system in the boar testis, suggesting that the testis act as a source and possible target tissue of RLN.

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Increased Expression of the Relaxin Receptor (LGR7) in Human Endometrium during the Secretory Phase of the Menstrual Cycle

Cited by 19 publications

References 30 publications

Expression of RXFP1 Is Decreased in Idiopathic Pulmonary Fibrosis. Implications for Relaxin-based Therapies

Expression of RXFP1 Is Decreased in Idiopathic Pulmonary Fibrosis. Implications for Relaxin-based Therapies

International Union of Basic and Clinical Pharmacology. XCV. Recent Advances in the Understanding of the Pharmacology and Biological Roles of Relaxin Family Peptide Receptors 1–4, the Receptors for Relaxin Family Peptides

Evidence for expression of relaxin hormone-receptor system in the boar testis

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