Relaxin Stimulates Uterine Edema via Activation of Estrogen Receptors: Blockade of its Effects Using ICI 182,789, a Specific Estrogen Receptor Antagonist

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