Intersection of the relaxin and estrogen signalling pathways in the uterus

The protein hormone relaxin exerts a wide range of effects on the reproductive system, as well as other tissues, including stimulation of growth of the uterus during pregnancy, remodelling of the reproductive tract in preparation for parturition, and development of the mammary glands [1]. The mechanisms by which relaxin exerts these effects, however, remain unclear, in large part because the relaxin receptor has not yet been cloned. Interestingly, many of relaxin’s acute effects on the uterus closely resemble those induced by estrogens. For example, relaxin rapidly induces a large increase in uterine wet weight in immature, ovariectomized rats, and also stimulates uterine metabolic processes, regardless of whether or not there is prior estrogen priming [2–5]. Uterine growth is also stimulated in other species, including pigs [6–8] and primates [9,10]. Estrogen and relaxin can induce the expression of many of the same genes, including vascular endothelial growth factor [VEGF; 11,12, Pillai SB et al., this volume], insulin-like growth factor I [IGF-I; 7,13], the uterine transcription factor HOXA-10 [14], and endothelial-type NO synthase [15–17], all of which could play roles in mediating relaxin’s uterotrophic effects.