Estrogen Affects the Cellular Metabolism of the Anterior Cruciate Ligament: A Potential Explanation for Female Athletic Injury

Abstract

Investigations from this laboratory have established the presence of estrogen receptors in the human an terior cruciate ligament. This study further investigates the effects of 17β-estradiol on the cellular proliferation and collagen synthesis of fibroblasts derived from the rabbit anterior cruciate ligament. Fibroblast prolifera tion and collagen synthesis in response to near log concentrations of 17β-estradiol (at 0.0029, 0.025, 0.25, 2.5, and 25 ng/ml) were assessed by measuring [3 H]thymidine and [14 C]hydroxyproline incorporation, respectively. Collagen synthesis was significantly re duced with increasing local estradiol concentration (P < 0.001). Declining collagen synthesis was first noted at a 17β-estradiol concentration of 0.025 ng/ml. Within normal physiologic levels of estrogen (0.025 to 0.25 ng/ml), collagen synthesis was reduced by more than 40% of control, and at pharmacologic levels of 2.5 and 25 ng/ml, by more than 50% of control. A signifi cant reduction of fibroblast proliferation was also ob served with increasing estradiol concentrations (P = 0.023). Clinically, alterations in anterior cruciate liga ment cellular metabolism caused by estrogen fluctua tions may change the composition of the ligament, rendering it more susceptible to injury.