Immunohistochemical demonstration of relaxin in the genital tract of men

Yki‐Järvinen, Hannele; Wahlström, Torsten; Seppälä, Markku

doi:10.1530/jrf.0.0690693

Cited by 36 publications

(20 citation statements)

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“…Unlike its effects on body growth, the finding that relaxin regulates the male reproductive tract confirms the findings of earlier investigations that demonstrated male reproductive tissues as being targets for relaxin activity (Brenner et al, 1984;Carrell et al, 1995;Essig et al, 1982;Ivell et al, 1989;Min and Sherwood, 1998;Weiss, 1989;Winslow et al, 1992;Yki-Jarvinen et al, 1983). Relaxin was previously identified in the seminal plasma of humans (Weiss, 1989;Winslow et al, 1992) in the peripheral circulation of boars (Juang et al, 1996) and was shown to enhance the penetration of human sperm into human or bovine cervical mucus (Brenner et al, 1984).…”

Section: Discussionsupporting

confidence: 84%

“…Furthermore, reports of additional actions of relaxin in tissues (Tan et al, 1999) and cells (Parsell et al, 1996;Unemori and Amento, 1990;Wyatt et al, 2002) outside the female reproductive tract and the localization of relaxin binding sites in the heart and brain (Osheroff et al, 1992;Osheroff and Ho, 1993;Osheroff and Phillips, 1991) have expanded the role of relaxin from a hormone of pregnancy to a growth factor/cytokine. Immunoreactive relaxin and relaxin-binding sites have also been detected within the male reproductive tract: in the prostate (Ivell et al, 1989;Yki-Jarvinen et al, 1983), the seminal fluid (Essig et al, 1982;Weiss et al, 1986;Winslow et al, 1992), testis (Min and Sherwood, 1998), and spermatozoa (Carrell et al, 1995). In contrast to mammals where relaxin is produced in the prostate (Ivell et al, 1989;Yki-Jarvinen et al, 1983), the testis appears to be the major source of relaxin in some species (Steinetz et al, 1998).…”

mentioning

confidence: 99%

“…Immunoreactive relaxin and relaxin-binding sites have also been detected within the male reproductive tract: in the prostate (Ivell et al, 1989;Yki-Jarvinen et al, 1983), the seminal fluid (Essig et al, 1982;Weiss et al, 1986;Winslow et al, 1992), testis (Min and Sherwood, 1998), and spermatozoa (Carrell et al, 1995). In contrast to mammals where relaxin is produced in the prostate (Ivell et al, 1989;Yki-Jarvinen et al, 1983), the testis appears to be the major source of relaxin in some species (Steinetz et al, 1998). From these initial findings, it was suggested that relaxin may be involved in increasing sperm motility (Weiss, 1989) and enhancing the ability of sperm to penetrate the cervical mucus (Brenner et al, 1984).…”

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Relaxin Is a Key Mediator of Prostate Growth and Male Reproductive Tract Development

Samuel

Tian

Zhao

et al. 2003

Laboratory Investigation

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SUMMARY:Male mice deficient in relaxin showed retarded growth and marked deficiencies in the reproductive tract within 1 month of age. At 3 months of age, male reproductive organ weight (including the testis, epididymis, prostate, and seminal vesicle) from relaxin null (RLXϪ/Ϫ) mice were significantly (p Ͻ 0.05) smaller than those of wild-type (RLXϩ/ϩ) male mice. Histologic examination of RLXϪ/Ϫ mouse tissues demonstrated decreased sperm maturation (testis), increased collagen, and decreased epithelial proliferation in the prostate compared with tissues obtained from RLXϩ/ϩ animals. The degree of sperm maturation in the testes of sexually mature RLXϪ/Ϫ mice (3 months) resembled that of immature (1 month) RLXϩ/ϩ mice and correlated with a decrease in fertility in RLXϪ/Ϫ mice. The marked differences in the extracellular matrix of the testis and prostate in RLXϪ/Ϫ males also correlated with an increase in the rate of cell apoptosis. Relaxin and LGR7 (relaxin receptor) mRNA expression was demonstrated in the prostate gland and testis of the normal mouse. Data from this study demonstrate that relaxin is an important factor in the development and function of the male reproductive tract in mice and has an essential role in the growth of the prostate and maintenance of male fertility. Relaxin may mediate its effects on growth and development by serving as an antiapoptotic factor. (Lab Invest 2003, 83:1055-1067.

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Section: Discussionsupporting

confidence: 84%

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confidence: 99%

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confidence: 99%

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Relaxin Is a Key Mediator of Prostate Growth and Male Reproductive Tract Development

Samuel

Tian

Zhao

et al. 2003

Laboratory Investigation

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“…To confirm an increased expression of relaxin at the protein level in cancer cells, we analyzed the expression of relaxin protein in tissue microarrays by immunohistochemistry using a specific antihuman RLN2 antibody (22). Relaxin expression was present in both normal glandular epithelial cells and cancer cells as reported previously (5,6). However, there was significant Fig.…”

Section: Resultsmentioning

confidence: 54%

Relaxin Promotes Prostate Cancer Progression

Feng

Agoulnik²,

Bogatcheva

et al. 2007

Clinical Cancer Research

107

101

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Purpose:To understand the role of relaxin peptide in prostate cancer, we analyzed the expression of relaxin and its receptor in human prostate cancer samples, the effects of relaxin signaling on cancer cell phenotype in vitro, and the effects of increased serum relaxin concentrations on cancer progression in vivo. Experimental Design: The relaxin and its receptor leucine-rich repeat containing G proteinĉ oupled receptor 7 (LGR7) expression were studied by quantitative reverse transcription-PCR (11 benign and 44 cancer tissue samples) and by relaxin immunohistochemistry using tissue microarrays containing 10 normal and 69 cancer samples. The effects of relaxin treatment and endogenous relaxin/LGR7 suppression via short interfering RNA in PC-3 and LNCaP cells were analyzed in vitro. The effect of transgenic relaxin overexpression [Tg(Rln1)] on cancer growth and survival was evaluated in autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP). Results: The relaxin mRNA expression was significantly higher in recurrent prostate cancer samples. In tissue microarrays of the 10 normal tissues, 8 had low staining in epithelial cells, whereas only 1of 9 high-grade prostatic intraepithelial neoplasia lesions had low expression (P = 0.005) and only 29 of 65 cancers had low expression (P = 0.047). Stimulation with relaxin increased cell proliferation, invasiveness, and adhesion in vitro. The suppression of relaxin/LGR7 via short interfering RNAs decreased cell invasiveness by 90% to 95% and growth by 10% to 25% and increased cell apoptosis 0.6 to 2.2 times. TheTg(Rln1) TRAMP males had shorter median survival time, associated with the decreased apoptosis of tumor cells, compared with non-Tg(Rln1) TRAMP animals. Conclusions: Relaxin signaling plays a role in prostate cancer progression.Prostate cancer is the second most common malignancy in men in Western countries. After advancing to the androgenindependent stage, prostate cancer is unresponsive to androgen ablation therapy and is refractory (1). Identification of novel endogenous factors responsible for proliferation, survival, and migration of the prostate cancer cells may generate new therapeutic targets for treatment.Relaxin is a short circulating peptide hormone (2, 3). Two highly homologous genes on human chromosome 9 encode RLN1 and RLN2 peptides with predicted 82% identity at amino acid level. In the corpus luteum, the main source of circulating relaxin in females, only RLN2 is expressed (2 -4). Prostate is the main site of relaxin expression in men (5 -7). Relaxin, secreted from the prostate gland into seminal fluid, is the product of the RLN2 gene; however, the expression of both RLN1 and RLN2 genes has been detected in prostate at mRNA level (8). In nonprimates, there is only one orthologous RLN1 gene. Related peptides, such as RLN3 or INSL3, have a more restricted expression pattern (3). It has been shown that relaxin plays a role in connective tissue remodeling, suppression of fibrosis, dilation of blood vessels, and angiogenesis (2, 3). Th...

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“…In most species, the prostate is the main source of the hormone (reviewed in Sherwood (1994Sherwood ( , 2004). In humans, the relaxin gene and protein are expressed in the prostate (Sokol et al 1989, Gunnersen et al 1996, Garibay-Tupas et al 2000, but relaxin immunoreactivity is also present in the seminal vesicles and the ampular region of the vas deferens (Yki-Järvinen et al 1983). In the boar, the seminal vesicle seems to be the main source of the hormone (Kohsaka et al 1992), although a relaxin-like antigen may also be present in the testis (Dubois & Dacheux 1978).…”

Section: Introductionmentioning

confidence: 99%

Locally produced relaxin may affect testis and vas deferens function in rats

Cardoso¹,

Nascimento²,

Royer³

et al. 2010

Reproduction

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We have previously shown that the rat testis and vas deferens contain high levels of the relaxin receptor, RXFP1. The present study was undertaken to determine the expression of relaxin in these tissues, and the effect of exogenous relaxin on Sertoli cell proliferation and on the mRNA levels of some proteins that may contribute to epithelial secretion and tissue reorganization in the vas deferens. Relaxin mRNA levels in testis and vas deferens were much lower than in the prostate. Sertoli cells seem to be an important source of relaxin mRNA in testis. Relaxin immunoreactivity was detected in the seminiferous epithelium but not in the interstitial compartment. The relaxin precursor was expressed in the vas deferens, and relaxin immunoreactivity was detected in apical cells of the vas deferens. Castration, but not treatment with the anti-estrogen ICI 182,780, dramatically reduced relaxin mRNA levels in the prostate and vas deferens, and this effect was prevented by testosterone. Rxfp1 mRNA levels in the vas deferens and prostate were not affected by castration or treatment with ICI 182,780. Exogenous relaxin increased the incorporation of 3 H-thymidine in cultured Sertoli cells, and treatment of the vas deferens with 100 ng/ml relaxin increased the mRNA levels for the cystic fibrosis chloride channel (cystic fibrosis transmembrane regulator) about three times, and doubled mRNA levels for the inducible form of nitric oxide synthase and metalloproteinase 7. These results suggest that locally produced relaxin acts as an autocrine or paracrine agent in the testis and vas deferens to affect spermatogenesis and seminal fluid composition.

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Immunohistochemical demonstration of relaxin in the genital tract of men

Cited by 36 publications

References 14 publications

Relaxin Is a Key Mediator of Prostate Growth and Male Reproductive Tract Development

Relaxin Is a Key Mediator of Prostate Growth and Male Reproductive Tract Development

Relaxin Promotes Prostate Cancer Progression

Locally produced relaxin may affect testis and vas deferens function in rats

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