Introduction and hypothesis This study evaluates the expression of estrogen receptor isoforms alpha (ER alpha) and beta (ER beta), progesterone receptor (PR), and relaxin receptor isoforms 1 and 2 (LGR7, LGR8) in uterosacral ligament (USL) tissue of women with pelvic organ prolapse and controls. Methods Tissue samples of USL from women with and without pelvic organ prolapse (POP) were subjected to immunohistochemistry against ER alpha, ER beta, PR, and LGR7 proteins. The respective mRNA expression as well as of LGR8 was assessed by quantitative real-time polymerase chain reaction. Results The cellular distribution of the receptor proteins was different due to cell types, independent of POP: ER alpha and PR were found in smooth muscle cells, but not in endothelial cells, whereas ER beta was found in endothelial cells, but not in connective tissue. ER alpha, ER beta, PR, and LGR7 mRNAs could be detected in all patients of both groups. ER alpha mRNA expression was significantly and ER beta mRNA borderline significantly higher in USL of patients with POP: ER alpha: p<0.001, ER beta: p=0.057. Conclusions Enhanced effects of estrogen via altered mRNA expression patterns of ER alpha and ER beta-but not those of progesterone-may exist in USL of patients affected by POP. A local effect of relaxin needs to be further clarified because of this first report of prevalent ligamental expression of LGR7.