The purpose of this proposal is to further our understanding of the actions and control of human relaxin in both genders. Relaxin is a product of the human corpus luteum of pregnancy and human decidua. It is hypothesized that relaxin is one of the regulators of maternal homeostasis. The effect of corpus luteum number and hCG concentrations on circulating relaxin will be determined. We hypothesize that the hyperrelaxinemia seen in multiple pregnancies and after some superovulation protocols is a cause of premature cervical ripening and premature labor. This hypothesis will be tested in triplet pregnancies and pregnancies resulting from superovulation. Determination of a relationship between prematurity and hyperrelaxinemia may provide new insights into the control and prevention of prematurity. Relaxin may help prepare the pregnant women for parturition and nursing. Proposed studies will determine the effects of relaxin on maternal growth hormone and prolactin secretion. Relaxin is present in human milk. The source and stimuli of milk relaxin secretion will be determined. The effect of potential stimulators and inhibitors of decidual relaxin secretion will be determined in vitro. The control of relaxin secretion will be studied in hCG stimulated human luteinized granulosa cells. Relaxin is produced by the prostate gland, is present in seminal plasma and stimulates sperm motility. The mechanism of action of relaxin on sperm will be determined by studying relaxin receptors and the effect of relaxin on intracellular calcium and pH. The efficacy of relaxin in improving pregnancy rate when added to insemination media for intrauterine insemination will be determined. We hypothesize that this addition of relaxin will increase pregnancy rate and provide a new physiologic therapy for male infertility. These proposed physiological and clinical studies will increase our understanding of the control of pituitary hormone secretion during pregnancy, the role of relaxin in normal pregnancy, the control of relaxin production, the pathological effects of its hypersecretion, the mechanism of its action and its potential usefulness in the therapy of male infertility.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
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Reproductive Biology Study Section (REB)
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University of Medicine & Dentistry of NJ
Obstetrics & Gynecology
Schools of Medicine
United States
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Morelli, Sara S; Petraglia, Felice; Weiss, Gerson et al. (2010) Endometrial expression of relaxin and relaxin receptor in endometriosis. Fertil Steril 94:2885-7
Goldsmith, Laura T; Weiss, Gerson (2009) Relaxin in human pregnancy. Ann N Y Acad Sci 1160:130-5
Maseelall, Priya B; Seungdamrong, Aimee; Weiss, Gerson et al. (2009) Expression of LGR7 in the primate corpus luteum implicates the corpus luteum as a relaxin target organ. Ann N Y Acad Sci 1160:147-51
Weiss, Gerson; Goldsmith, Laura T (2005) Mechanisms of relaxin-mediated premature birth. Ann N Y Acad Sci 1041:345-50
Goldsmith, Laura T; Weiss, Gerson (2005) Relaxin regulates endometrial structure and function in the rhesus monkey. Ann N Y Acad Sci 1041:110-7
McGovern, Peter G; Llorens, Amaury J; Skurnick, Joan H et al. (2004) Increased risk of preterm birth in singleton pregnancies resulting from in vitro fertilization-embryo transfer or gamete intrafallopian transfer: a meta-analysis. Fertil Steril 82:1514-20
Goldsmith, Laura T; Weiss, Gerson; Palejwala, Smita et al. (2004) Relaxin regulation of endometrial structure and function in the rhesus monkey. Proc Natl Acad Sci U S A 101:4685-9
Palejwala, Smita; Tseng, Linda; Wojtczuk, Andrea et al. (2002) Relaxin gene and protein expression and its regulation of procollagenase and vascular endothelial growth factor in human endometrial cells. Biol Reprod 66:1743-8
Weiss, G; Goldsmith, L T (2001) Relaxin and the cervix. Front Horm Res 27:105-12
Iams, J D; Goldsmith, L T; Weiss, G (2001) The preterm prediction study: maternal serum relaxin, sonographic cervical length, and spontaneous preterm birth in twins. J Soc Gynecol Investig 8:39-42

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