Functional calcium-sensing receptor expression in ovarian surface epithelial cells

Objective: Our purpose was to determine whether human ovarian surface epithelial cells express calcium-sensing receptors and whether changes in extracellular calcium modulate the proliferation of these cells. Study design: Ovarian surface epithelial cells from normal patients and from ovarian tumors were tested for calcium-sensing receptor expression by Northern hybridization and immunoblot analysis. Functional responses to agonists of the calcium-sensing receptor were monitored by inositol triphosphate analysis and measurements of intracellular calcium release. The effect of extracellular calcium on proliferation was monitored by thymidine incorporation and growth curve analysis. Results: Increasing extracellular calcium above 0.8 mmol/L produces a marked proliferative response in normal ovarian surface epithelial cells. Both normal and transformed cells express calcium-sensing receptor messenger ribonucleic acid and protein; some tumor lines overexpress calcium-sensing receptor messenger ribonucleic acid. The calcium-sensing receptors in normal ovarian surface epithelial cells respond to the agonist gadolinium with increases in inositol triphosphate production and calcium release. Conclusion: Human ovarian surface epithelial cells are growth regulated by extracellular calcium, and calcium-sensing receptors may mediate this response.