Relaxin stimulates uterine edema via activation of estrogen receptors: Blockade of its effects using ICI 182,780, a specific estrogen receptor antagonist

Relaxin's ability to stimulate uterine growth is well established. The mech anisms by which relaxin exerts this effect, however, remain unclear. In lig ht of previous work demonstrating peptide growth factor activation of estro gen receptors (ERs), the present study was conducted to determine if relaxi n similarly stimulates ERs. Twenty-five day-old female Sprague-Dawley rats were bilaterally ovariectomized and treated with estradiol or porcine relax in alone or in combination with the ER antagonist ICI 182,780. Following tr eatment with 17 beta-estradiol or relaxin atone, the uterine weight;body we ight ratio (UtW/BW) increased significantly over control values (+98% and 77% respectively, p<0.0003). Pre-treatment of animals with ICI 182,780 (3 m u g/g BW) prior to either estradiol or relaxin treatment completely inhibit ed the hormone-induced increases in uterine weight (p<0.0005). ICI 182,780 alone had no significant effect Histological analysis of uterine cross-sect ions revealed that the edema present in the endometrium of animals treated with estradiol or relaxin alone was completely absent in the uteri of anima ls pre-treated with ICI 182,780. These data indicate that relaxin-induced u terine edema and growth is mediated by ERs.