Regulation of the reproductive cycle and early pregnancy by relaxin family peptides

Anand‐Ivell, Ravinder; Ivell, Richard

doi:10.1016/j.mce.2013.08.010

Cited by 36 publications

(22 citation statements)

References 104 publications

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“…RXFP1 is expressed in sperm in both mice (Krajnc-Franken et al, 2004) and humans (Carrell et al, 1995;Ferlin et al, 2012) and increases sperm motility and facilitates penetration into oocytes (Weiss, 1989). Another potential role for seminal relaxin may be to act on the female reproductive tract to prepare the endometrium for implantation (Telgmann and Gellersen, 1998;Unemori et al, 1999;Anand-Ivell and Ivell, 2014).…”

Section: Physiologic Roles Of Relaxin Family Peptide Receptors Andmentioning

confidence: 99%

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

121

118

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Section: Physiologic Roles Of Relaxin Family Peptide Receptors Andmentioning

confidence: 99%

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

121

118

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“…In females INSL3 is found at lower levels than in males, but it is detectable in serum and is largely produced in the theca interna cells of ovarian antral follicles in humans 8 . The role of ovarian INSL3 in humans is currently unknown however animal studies have demonstrated putative roles for thecal derived INSL3 in germ cell survival 9 and follicular androgen production 10 . In addition to its reproductive roles, INSL3 has been implicated in bone metabolism in males where low levels are associated with an increased risk of osteopenia and osteoporosis 11 .…”

Section: Introductionmentioning

confidence: 99%

Distinct activation modes of the Relaxin Family Peptide Receptor 2 in response to insulin-like peptide 3 and relaxin

Bruell

Sethi

Smith

et al. 2017

Sci Rep

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Relaxin family peptide receptor 2 (RXFP2) is a GPCR known for its role in reproductive function. It is structurally related to the human relaxin receptor RXFP1 and can be activated by human gene-2 (H2) relaxin as well as its cognate ligand insulin-like peptide 3 (INSL3). Both receptors possess an N-terminal low-density lipoprotein type a (LDLa) module that is necessary for activation and is joined to a leucine-rich repeat domain by a linker. This linker has been shown to be important for H2 relaxin binding and activation of RXFP1 and herein we investigate the role of the equivalent region of RXFP2. We demonstrate that the linker’s highly-conserved N-terminal region is essential for activation of RXFP2 in response to both ligands. In contrast, the linker is necessary for H2 relaxin, but not INSL3, binding. Our results highlight the distinct mechanism by which INSL3 activates RXFP2 whereby ligand binding mediates reorientation of the LDLa module by the linker region to activate the RXFP2 transmembrane domains in conjunction with the INSL3 A-chain. In contrast, relaxin activation of RXFP2 involves a more RXFP1-like mechanism involving binding to the LDLa-linker, reorientation of the LDLa module and activation of the transmembrane domains by the LDLa alone.

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“…Lgr-related genes are also present in humans and include those encoding relaxin-family peptide receptors RXFP1 and RXFP2, which among other functions are necessary for normal reproduction in both sexes (reviewed in ref. 23).…”

mentioning

confidence: 99%

Sex-specific regulation of Lgr3 in Drosophila neurons

Meissner

Luo

Dias

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The development of sexually dimorphic morphology and the potential for sexually dimorphic behavior in Drosophila are regulated by the Fruitless (Fru) and Doublesex (Dsx) transcription factors. Several direct targets of Dsx have been identified, but direct Fru targets have not been definitively identified. We show that Drosophila leucine-rich repeat G protein-coupled receptor 3 (Lgr3) is regulated by Fru and Dsx in separate populations of neurons. Lgr3 is a member of the relaxin-receptor family and a receptor for Dilp8, necessary for control of organ growth. Lgr3 expression in the anterior central brain of males is inhibited by the B isoform of Fru, whose DNA binding domain interacts with a short region of an Lgr3 intron. Fru A and C isoform mutants had no observed effect on Lgr3 expression. The female form of Dsx (Dsx F ) separately up-and down-regulates Lgr3 expression in distinct neurons in the abdominal ganglion through female-and male-specific Lgr3 enhancers. Excitation of neural activity in the Dsx F -up-regulated abdominal ganglion neurons inhibits female receptivity, indicating the importance of these neurons for sexual behavior. Coordinated regulation of Lgr3 by Fru and Dsx marks a point of convergence of the two branches of the sex-determination hierarchy.M ost animal species are comprised of female and male individuals, in which sex differences in form and behavior are specified by their genetic makeup. The developmental processes by which genes build sex-specific differences into the nervous system, and hence encode the potential for sex-specific behavior, have long been of interest (1).In Drosophila melanogaster the assessment of the number of X chromosomes leads to sex-differential splicing of transcripts from genes making up the sex-determination hierarchy, in particular the terminal genes of that hierarchy, fruitless (fru) and doublesex [dsx (2), reviewed in ref. 3]. fru and dsx encode sexspecific Zn-finger transcription factors that alter, either directly or indirectly, the expression of downstream genes to produce the sexually dimorphic elements of flies. The male-specific forms of Fru (Fru M ) act in a subset of the neurons within the male's nervous system to establish the potential for social interactions such as courtship behavior and aggression (reviewed in ref.3). In contrast, Dsx acts in subsets of both neural and nonneural tissues of males and females to regulate behavioral and nonbehavioral aspects of sexual development (reviewed in ref.3).Although the mechanisms regulating the production of the sexspecific isoforms of the Fru and Dsx proteins are well-established (4), how these proteins in turn function is only beginning to be elucidated. Several direct Dsx targets and a well-conserved 13-bp Dsx binding site have been identified (5-13). Many Dsx target genes encode well-known transcription factors and cell-cell signaling molecules that function sex-nonspecifically in most tissues in which they are expressed. However, in other tissues, Dsx directs the sexspecific expression of these gene...

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Regulation of the reproductive cycle and early pregnancy by relaxin family peptides

Cited by 36 publications

References 104 publications

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

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

Distinct activation modes of the Relaxin Family Peptide Receptor 2 in response to insulin-like peptide 3 and relaxin

Sex-specific regulation of Lgr3 in Drosophila neurons

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