Expression of the human relaxin gene in the corpus luteum of the menstrual cycle and in the prostate

Ivell, Richard; Hunt, Nicholas H.; Khan-Dawood, Firyal S.; Dawood, M. Yusoff

doi:10.1016/0303-7207(89)90037-3

Cited by 91 publications

(67 citation statements)

References 13 publications

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“…(Ivell and Einspanier, 2002;Sherwood, 2004). Both isoforms are expressed in prostate; however, to date only the H2 isoform has been shown to be translated and secreted (Ivell et al, 1989;GaribayTupas et al, 2000;Samuel et al, 2003;Welsh et al, 2003). Our data demonstrate that H2 relaxin is highly upregulated at both the message and protein level in the p53 R273H mutant.…”

Section: Discussionmentioning

confidence: 51%

“…Relaxin H1 expression was also elevated in two of the p53 GOF mutant sublines (G245S and R273H), but not to the same extent as H2 relaxin. While relaxin H1 mRNA is expressed in a number of tissues, relaxin H1 protein expression patterns have not been described (Ivell et al, 1989;Garibay-Tupas et al, 2000;Ivell and Einspanier, 2002;Samuel et al, 2003). The microarray findings were validated by RT-PCR analysis, which confirmed that H2 relaxin mRNA is expressed by all of the p53 GOF mutant cells lines (G245S, R248W, R273H, R273C) in the absence of androgen (Figure 3c).…”

Section: P53 Gof Mutations Facilitate the Androgen-independent (Ai) Gmentioning

confidence: 68%

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The R273H p53 mutation can facilitate the androgen-independent growth of LNCaP by a mechanism that involves H2 relaxin and its cognate receptor LGR7

et al. 2006

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Mutations in p53 occur at a rate of approximately 70% in hormone-refractory prostate cancer (CaP), suggesting that p53 mutations facilitate the progression of CaP to androgen-independent (AI) growth. We have previously reported that transfection of p53 gain of function mutant alleles into LNCaP, an androgen-sensitive cell line, allows for AI growth of LNCaP in vitro. We herein confirm the in vivo relevance of those findings by demonstrating that the R273H p53 mutation (p53 R273H ) facilitates AI growth in castrated nude mice. In addition, we demonstrate that H2 relaxin is responsible for facilitating p53 R273H -mediated AI CaP. H2 relaxin is overexpressed in the LNCaP-R273H subline. Downregulation of H2 relaxin expression results in significant inhibition of AI growth, whereas addition of recombinant human H2 relaxin to parental LNCaP promotes AI growth. Inhibition of AI growth was also achieved by blocking expression of LGR7, the cognate receptor of H2 relaxin. Chromatin immunoprecipitation analysis was used to demonstrate that p53 R273H binds directly to the relaxin promoter, further confirming a role for H2 relaxin signaling in p53 R273H -mediated AI CaP. Lastly, we used a reporter gene assay to demonstrate that H2 relaxin can induce the expression of prostate-specific antigen via an androgen receptor-mediated pathway.

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Section: Discussionmentioning

confidence: 51%

Section: P53 Gof Mutations Facilitate the Androgen-independent (Ai) Gmentioning

confidence: 68%

The R273H p53 mutation can facilitate the androgen-independent growth of LNCaP by a mechanism that involves H2 relaxin and its cognate receptor LGR7

et al. 2006

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“…Total RNA was extracted from bovine corpora lutea at different phases of the ovarian cycle and, after denaturation with glyoxal, Separated by electrophoresis on a horizontal agarose gel in MOPS buffer before transferring to Hybond-N nylon membranes (Amersham-Buchler, Braunschweig, FRG) for hybridization (50). The COUP factor-specific fragment obtained by the amplification procedure described above was radioactively labelled by random primer extension (51) and used as hybridization probe.…”

Section: Mrthykitioti Iritcr/iwncc /I)utprinrinqmentioning

confidence: 99%

Mapping of the Bovine Oxytocin Gene Control Region: Identification of Binding Sites for Luteal Nuclear Proteins in the 5′ Non‐Coding Region of the Gene

Walther¹,

Wehrenberg²,

Brackmann³

et al. 1991

J Neuroendocrinology

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In view of the small number of hormone-producing cells, the factors regulating oxytocin gene expression in the classic site of synthesis, in the magnocellular neurons of the hypothalamus, have not yet been characterized. In the early bovine corpus luteurn there is a tissue-specific oxytocin expression involving many more cells. This tissue therefore was chosen as a experimental system to identify deoxyribonucleic acid elements and nuclear proteins involved in the regulation of oxytocin gene expression. 3.2 kb from the 5' non-coding region of the bovine oxytocin gene have been sequenced and subcloned fragments used as probes for gel retardation and footprinting experiments. Binding sites for luteal as well as more ubiquitous proteins were detected in the oxytocin promoter region and in an artiodactyl-specific dispersed repeated deoxyribonucleic acid element. A binding site in the promoter region with a superficial similarity to an estrogen-responsive element (-159 to -152) was shown not to bind this steroid hormone receptor but to bind two nuclear proteins alternatively. One is a luteal protein, the other a more general transcription factor belonging to the steroid hormone receptor superfamily and similar, if not identical to the COUP protein. This alternative binding of a tissue-and phase-specifically expressed protein or an ubiquitous factor to the same site in the oxytocin promoter suggests a role for these two proteins in the transient up-regulation and subsequent down-regulation of the oxytocin gene during the differentiation of the bovine corpus luteum.

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“…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%

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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Expression of the human relaxin gene in the corpus luteum of the menstrual cycle and in the prostate

Cited by 91 publications

References 13 publications

The R273H p53 mutation can facilitate the androgen-independent growth of LNCaP by a mechanism that involves H2 relaxin and its cognate receptor LGR7

The R273H p53 mutation can facilitate the androgen-independent growth of LNCaP by a mechanism that involves H2 relaxin and its cognate receptor LGR7

Mapping of the Bovine Oxytocin Gene Control Region: Identification of Binding Sites for Luteal Nuclear Proteins in the 5′ Non‐Coding Region of the Gene

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

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