Synthesis and function of relaxin in human endometrium

Weiss, Gerson; Palejwala, Smita; Tseng, Linda; Goldsmith, Laura T.

doi:10.1007/978-94-017-2877-5_4

Cited by 3 publications

(4 citation statements)

References 16 publications

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“…5). This decidual RLX isoform is thought to play a local, paracrine role in endometrial tissue differentiation and remodeling and in embryo accommodation (36). The results of the present study suggest an additional possible role for decidual RLX, as in normal pregnancies it could counterbalance the local activating factors for neutrophils.…”

Section: Discussionmentioning

confidence: 77%

Relaxin Inhibits the Activation of Human Neutrophils: Involvement of the Nitric Oxide Pathway

et al. 2004

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In animal models of inflammation, the pregnancy hormone relaxin was shown to reduce the recruitment of leukocytes, especially neutrophils, in inflamed tissues. The current study was designed to clarify whether relaxin could inhibit activation of isolated human neutrophils and, if so, whether the nitric oxide (NO) biosynthetic pathway was involved, as occurs in other relaxin targets. Human neutrophils were preincubated with 1, 10, and 100 nmol/liter porcine relaxin for 1 h before activation with N-formyl-Met-Leu-Phe (10 micromol/liter) or phorbol-12-myristate-13-acetate (0.1 micromol/liter). In selected experiments, the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 100 micromol/liter) was added to the samples 30 min before relaxin. In other experiments, chemically inactivated relaxin (10 nmol/liter) was substituted for authentic relaxin. Untreated, nonactivated neutrophils were the controls. Relaxin reduced significantly and in a concentration-dependent fashion the expression of the surface activation marker CD11b, as well as the generation of superoxide anion, the rise of intracellular Ca(2+), the release of cytoplasmic granules, and the chemotactic migration. These effects of relaxin were blunted by N(G)-monomethyl-L-arginine and could not be reproduced by inactivated relaxin. Relaxin also increased neutrophil inducible NO synthase expression and NO generation. This study provides evidence that relaxin inhibits the activation of human neutrophils stimulated by different proinflammatory agents. This novel property of relaxin could be of relevance in toning down maternal neutrophil activation during pregnancy, thereby counteracting the occurrence of pregnancy-related disorders such as preeclampsia, which is regarded as an excess maternal inflammatory response to pregnancy.

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Section: Discussionmentioning

confidence: 77%

Relaxin Inhibits the Activation of Human Neutrophils: Involvement of the Nitric Oxide Pathway

et al. 2004

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“…It is unclear if relaxin has any role in placental production of sFlt-1 and sEng. However, as mentioned previously, relaxin is known to enhance VEGF production 33,53,76 and has been demonstrated to attenuate vascular responses to angiotensin II in animal models. 159,160 In addition, women with ovarian failure have abnormal renal vascular adaptations to pregnancy compared to women with normal ovarian function by week 7 of gestation.…”

Section: Preeclampsiamentioning

confidence: 86%

“…90 Relaxin is a known stimulant of VEGF in human endometrial stromal and glandular epithelial cells in a dose-dependent manner in vitro. 33,53,76 Relaxin also acts on connective tissue to modify expression of MMPs and their inhibitors (TIMPs). Human dermal fibroblasts treated with relaxin secreted increased levels of MMPs, while decreasing expression of TIMPs.…”

Section: Implantationmentioning

confidence: 99%

“…[30][31][32] To date, there are no obvious clinical conditions associated with a relaxin deficiency in pregnant women. 33,34 However, women with reduced circulating relaxin in early pregnancy have a history of recurrent miscarriage 35 and have an increased risk of developing preeclampsia. 36,37 In addition, few studies have considered the potential contribution of relaxin to gynecological disorders.…”

Section: Introductionmentioning

confidence: 99%

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The Role of Relaxin in Normal and Abnormal Uterine Function During the Menstrual Cycle and Early Pregnancy

et al. 2017

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The hormone relaxin is a 6-kDa peptide with high structural similarity to insulin. It is primarily produced by the corpus luteum during pregnancy but is also synthesized by other reproductive organs such as the uterus, decidua, and placenta. Relaxin binds to its receptor RXFP1, which has been localized to a wide variety of reproductive and nonreproductive tissues. The peptide's many uterotropic effects include stimulating uterine growth and vascularization, remodeling extracellular matrix components, and regulating vascular endothelial growth factor in preparation for implantation. Evidence also supports a role for relaxin in the systemic maternal vascular adaptations required for a healthy pregnancy. Diminished relaxin levels in early pregnancy are linked with increased risks of miscarriage and the development of preeclampsia. In addition to pregnancy, relaxin may also play a functional role in the uterus during the menstrual cycle, and modified relaxin activity may contribute to gynecological disorders such as uterine fibrosis and endometriosis. Despite over 75 years of research, we still have a limited understanding of relaxin's broad roles in the uterus, particularly as there are significant species differences in its synthesis and activity, which restricts the use of animal models for human-centric questions. Here, we review current knowledge regarding relaxin actions in the human uterus during the menstrual cycle and in early pregnancy, with a focus on its potential roles in various gynecological disorders, as well as the pregnancy disorders such as preeclampsia, recurrent miscarriage, and early pregnancy loss.

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Relaxin Physiology in the Female Reproductive Tract during Pregnancy

Parry

Vodstrcil

Advances in Experimental Medicine and Biology

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The characteristic functions of relaxin are associated with female reproductive tract physiology. These include the regulation of biochemical processes involved in remodeling the extracellular matrix of the cervix and vagina during pregnancy and rupture of the fetal membranes at term. Such modifications enable the young to move unimpeded through the birth canal and prevent dystocia. However, relaxin's physiological actions are not limited to late gestation. New functions for this peptide hormone in implantation and placentation are also emerging. Relaxin promotes uterine and placental growth and influences vascular development and proliferation in the endometrium. This chapter provides an overview of the current literature on relaxin physiology in the uterus, cervix and vagina of pregnant females and the impact on fetal health. It also outlines the potential mechanisms of relaxin action, particularly in the cervical extracellular matrix and uterine endometrium.

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Synthesis and function of relaxin in human endometrium

Cited by 3 publications

References 16 publications

Relaxin Inhibits the Activation of Human Neutrophils: Involvement of the Nitric Oxide Pathway

Relaxin Inhibits the Activation of Human Neutrophils: Involvement of the Nitric Oxide Pathway

The Role of Relaxin in Normal and Abnormal Uterine Function During the Menstrual Cycle and Early Pregnancy

Relaxin Physiology in the Female Reproductive Tract during Pregnancy

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