Biology of the relaxin-like factor (RLF)

Ivell, R

doi:10.1530/revreprod/2.3.133

Cited by 17 publications

(29 citation statements)

References 5 publications

(10 reference statements)

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“…A polyadenylation signal is present in the 3Ј-untranslated region of both genes, in a position 582 and 448 bp downstream from an in-frame TAG stop codon for the human and mouse genes, respectively. A single intron interrupts the coding region in an identical position in the sequence of both genes, corresponding to a similar position to that of other relaxin and insulin family members (2,30,33). The H3 relaxin gene is localized on chromosome 19 at 19p13.3, whereas the mouse gene is located on chromosome 8 at 8C2.…”

Section: Characterization Of H3 and M3 Relaxin Gene Sequences-mentioning

confidence: 99%

“…Synthetic H3 relaxin was also tested for its ability to compete for 33 P-labeled H2 relaxin binding to relaxin-binding sites in THP-1 cells (Fig. 3B), with an affinity (pK i ϭ 7.5 Ϯ 0.16; n ϭ 3) lower than that of H2 (pK i ϭ 8.74 Ϯ 0.11; n ϭ 11) and H1 (pK i ϭ 9.0 Ϯ 0.11; n ϭ 7) relaxin.…”

Section: Characterization Of H3 and M3 Relaxin Gene Sequences-mentioning

confidence: 99%

“…The cells were incubated in binding buffer with 33 P-labeled H2 (B33) relaxin (100 pM), labeled as previously described (11) at 25°C for 90 min in the absence or presence of increasing concentrations of unlabeled H1, H2 and H3 relaxin (100 pM to 30 nM)). Nonspecific binding was defined with H2 relaxin (1 M).…”

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confidence: 99%

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Human Relaxin Gene 3 (H3) and the Equivalent Mouse Relaxin (M3) Gene

Bathgate

Samuel

Burazin

et al. 2002

Journal of Biological Chemistry

358

396

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We have identified a novel human relaxin gene, designated H3 relaxin, and an equivalent relaxin gene in the mouse from the Celera Genomics data base. Both genes encode a putative prohormone sequence incorporating the classic two-chain, three cysteine-bonded structure of the relaxin/insulin family and, importantly, contain the RXXXRXX(I/V) motif in the B-chain that is essential for relaxin receptor binding. A peptide derived from the likely proteolytic processing of the H3 relaxin prohormone sequence was synthesized and found to possess relaxin activity in bioassays utilizing the human monocytic cell line, THP-1, that expresses the relaxin receptor. The expression of this novel relaxin gene was studied in mouse tissues using RT-PCR, where transcripts were identified with a pattern of expression distinct from that of the previously characterized mouse relaxin. The highest levels of expression were found in the brain, whereas significant expression was also observed in the spleen, thymus, lung, and ovary. Northern blotting demonstrated an ϳ1.2-kb transcript present in mouse brain poly(A) RNA but not in other tissues. These data, together with the localization of transcripts in the pars ventromedialis of the dorsal tegmental nucleus of C57BLK6J mouse brain by in situ hybridization histochemistry, suggest a new role for relaxin in neuropeptide signaling processes. Together, these studies describe a third member of the human relaxin family and its equivalent in the mouse.Relaxin is a 6-kDa polypeptide hormone that is secreted by the ovary into the peripheral circulation in highest amounts during pregnancy and has a number of functions in mammals that are generally associated with female reproductive tract physiology (1). To date, only one relaxin gene has been characterized in most mammalian species, with the exception of the human where two separate genes have been described, designated H1 (2) and H2 (3) relaxin. The peptide encoded by the H2 gene is the major stored and circulating form in the human (4). H1 relaxin expression is restricted to the decidua, placenta, and prostate (5); however, the H1 peptide has similar biological activity to that of H2 relaxin in a rat atrial bioassay (6). The actions of relaxin include an ability to inhibit myometrial contractions, to stimulate remodeling of the connective tissue, and to induce softening of the tissues of the birth canal. Additionally, relaxin increases growth and differentiation of the mammary gland and nipple and induces the breakdown of collagen, one of the main components of connective tissue. Relaxin decreases collagen synthesis and increases the release of collagenases (7). These findings were recently confirmed by the establishment of the relaxin gene-knockout mouse (8), which exhibited a number of phenotypic properties associated with pregnancy. Female mice lacking a functionally active relaxin gene failed to relax and elongate the interpubic ligament of the pubic symphysis and could not suckle their pups, who in turn died within 24 h unless cross-fostered t...

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Section: Characterization Of H3 and M3 Relaxin Gene Sequences-mentioning

confidence: 99%

Section: Characterization Of H3 and M3 Relaxin Gene Sequences-mentioning

confidence: 99%

See 1 more Smart Citation

Human Relaxin Gene 3 (H3) and the Equivalent Mouse Relaxin (M3) Gene

Bathgate

Samuel

Burazin

et al. 2002

Journal of Biological Chemistry

358

396

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“…INSL3 in the ovary during the cycle and early pregnancy INSL3 (insulin-like peptide 3) is structurally very closely related to relaxin, and for this reason was originally referred to as the relaxin-like factor (RLF; Büllesbach et al, 1999;Ivell, 1997). It was originally identified as a major product of the testicular Leydig cells in the male by independent differential cloning strategies (Adham et al, 1993;Pusch et al, 1996).…”

Section: Insl3mentioning

confidence: 99%

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

Anand‐Ivell¹,

Ivell²

2014

Molecular and Cellular Endocrinology

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a b s t r a c tThe relaxin family of peptide hormones are structurally closely related to one another sharing a heterodimeric A-B structure, like that of insulin. They may also be active as unprocessed B-C-A pro-forms. Relaxin has been shown to pay a key role within the ovary, being involved in follicle growth, and ovulation. Relaxin is produced in large amounts also by the corpus luteum where it acts as an endocrine hormone positively affecting implantation, placentation and vascularization during the all-important first trimester phase of pregnancy establishment. Relaxin exerts its functions via the receptor RXFP1. Insulin-like peptide 3 (INSL3) in contrast acts through the related receptor RXFP2, and plays an essential role in the production of androgens within growing antral follicles. INSL3 is also produced in large amounts by the male fetus shortly after sex determination, where it controls the first transabdominal phase of testicular descent. However, this fetal INSL3 is also able to influence placental and maternal physiology, indicating associations with later preeclampsia and/or fetal growth restriction. Other members of this relaxin-like family of peptides, such as INSL4, INSL5 and INSL6 are less well studied, though all suggest modulatory roles in ovarian and/or placental function.

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“…Insulin-like peptide-3 (INSL3), also known as relaxin-like factor, belongs to the insulin/relaxin superfamily that now comprises at least ten members in mammals (Ivell 1997, Bathgate et al 2003, Hsu 2003. INSL3 is a developmentally regulated hormone with sexually dimorphic expression (Balvers et al 1998, Zimmermann et al 1999.…”

Section: Introductionmentioning

confidence: 99%

Leucine-rich repeat-containing G-protein-coupled receptor 8 in mature glomeruli of developing and adult rat kidney and inhibition by insulin-like peptide-3 of glomerular cell proliferation

Fu¹,

Shen²,

Zhao³

et al. 2006

Journal of Endocrinology

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Leucine-rich repeat-containing G-protein-coupled receptor 8 (LGR8, or RXFP2) is a member of the type C leucine-rich repeat-containing G protein-coupled receptor family, and its endogenous ligand is insulin-like peptide-3 (INSL3). Although LGR8 expression has been demonstrated in various human tissues, including testis, ovary, brain and kidney, the precise roles of this receptor in many of these tissues are unknown. In an effort to better understand INSL3-LGR8 systems in the rat, we cloned the full-length Lgr8 cDNA and investigated the presence and cellular localization of Lgr8 mRNA expression in adult and developing rat kidney. On the basis of these findings, we investigated the presence and distribution of renal 125 I-labelled human INSL3-binding sites and the nature of INSL3-LGR8 signalling in cultured renal cells. Thus, using in situ hybridization histochemistry, cells expressing Lgr8 mRNA were observed in glomeruli of renal cortex from adult rats and were tentatively identified as mesangial cells. Quantitative, real-time PCR analysis of the developmental profile of Lgr8 mRNA expression in kidney revealed highest relative levels at late stage gestation (embryonic day 18), with a sharp decrease after birth and lowest levels in the adult. During development, silver grains associated with Lgr8 mRNA hybridization were observed overlying putative mesangial cells in mature glomeruli, with little or no signal associated with less-mature glomeruli. In adult and developing kidney, specific 125 I-INSL3-binding sites were associated with glomeruli throughout the renal cortex. In primary cultures of glomerular cells, synthetic human INSL3 specifically and dose-dependently inhibited cell proliferation over a 48 h period, further suggesting the presence of functional LGR8 (receptors) on these cells (mesangial and others). These findings suggest INSL3-LGR8 signalling may be involved in the genesis and/or developmental maturation of renal glomeruli and possibly in regulating mesangial cell density in adult rat kidney.

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Biology of the relaxin-like factor (RLF)

Cited by 17 publications

References 5 publications

Human Relaxin Gene 3 (H3) and the Equivalent Mouse Relaxin (M3) Gene

Human Relaxin Gene 3 (H3) and the Equivalent Mouse Relaxin (M3) Gene

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

Leucine-rich repeat-containing G-protein-coupled receptor 8 in mature glomeruli of developing and adult rat kidney and inhibition by insulin-like peptide-3 of glomerular cell proliferation

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