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Relaxin Receptors in the Human Female Anterior Cruciate Ligament

Background Noncontact anterior cruciate ligament injuries occur two to eight times more often in women than in men. Changes in ligament laxity and strength have been associated with female hormones such as relaxin. Hypothesis Relaxin receptors are present within the female anterior cruciate ligament. Study Design Controlled laboratory study. Methods Remnants of anterior cruciate ligament were harvested from five women and five men undergoing routine ligament reconstruction. Relaxin was biotinylated and analyzed for biologic activity with use of the mouse interpubic ligament bioassay. Immunohistochemical localization of relaxin receptors was performed with appropriate negative controls and competitive binding assays to determine receptor specificity and saturability. Results Anterior cruciate ligament sections from women but not from men showed uniform specific binding that was limited to synovial lining cells, stromal fibroblasts, and cells lining blood vessels. Specific binding was confirmed in the presence of a 2000-fold excess of human insulin, the structural homolog of relaxin, and competitive inhibition was demonstrated in the presence of a 2000-fold excess of unlabeled relaxin. Conclusions Relaxin exhibits specific saturable binding in the female anterior cruciate ligament, where specific relaxin receptors were present. Clinical Relevance The high incidence of anterior cruciate ligament rupture in female athletes may be partially explained by the effects of relaxin.