Although the role of the reproductive
hormone,
relaxin, in rodents is well documented, its potential contribution to human reproduction is less well defined. In this study, we examine the effects of
relaxin on human endometrial cells in vitro and describe the clinical effects of
relaxin on menstrual flow in women. In cultured endometrial cells,
relaxin specifically induces the expression of an angiogenic agent,
vascular endothelial growth factor (
VEGF). cAMP is implicated as a second messenger involved in
VEGF stimulation.
VEGF expression is temporally regulated in the endometrium, and our results suggest that
relaxin, which is secreted by the corpus luteum and is present in the endometrium during the menstrual cycle and pregnancy, may be involved in regulating endometrial
VEGF expression.
Relaxin was recently tested in a clinical trial for efficacy in the treatment of
progressive systemic sclerosis, and was administered at levels up to 10 times higher than that measured during pregnancy. The most frequent
relaxin-related adverse event reported during the course of the study was the onset of menometrorrhagia, defined in this study as heavier-than-usual or irregular menstrual
bleeding. The intensification of menstrual flow observed in these patients is consistent with the hypothesis that
relaxin mediates neovascularization of the endometrial lining.