Relaxin stimulates expression of vascular endothelial growth factor in normal human endometrial cells in vitro and is associated with menometrorrhagia in women.
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.
Unemori
E N
EN
Connetics Corporation, Palo Alto, California 94303, USA.
Erikson
M E
ME
Rocco
S E
SE
Sutherland
K M
KM
Parsell
D A
DA
Mak
J
J
Grove
B H
BH
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004717:Endometrium / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008222:Lymphokines / Q000235:genetics*; D008595:Menorrhagia / Q000139:chemically induced*; D008796:Metrorrhagia / Q000139:chemically induced*; D008875:Middle Aged; D011247:Pregnancy; D012065:Relaxin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D015290:Second Messenger Systems; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D012065:Relaxin; D000242:Cyclic AMP