Abstract: 474

GONADOTROPIN REGULATION OF NORMAL OVARIAN SURFACE EPITHELIUM AND OVARIAN CANCER CELLS: IMPLICATIONS FOR OVARIAN CANCER.

Jeff Parrott^{1 *}, Grace Kim¹ , Vini Doraiswamy^{1 *}, Rachel Moser¹ , Michael Skinner^{1 *}
Center for Reproductive Biology, Dept. of Genetics and Cell Biology, Washington State University, Pullman, WA 99164 ¹

The gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH), are proposed to be involved in proliferation of ovarian surface epithelial (OSE) cells that may lead to ovarian cancer. Several observations support this hypothesis. Ovarian cancer is more common in conditions with elevated gonadotropins such as menopausal women or women who have received treatment for induction of ovulation. Reduced risk for ovarian cancer is associated with multiple pregnancies and breast feeding, oral contraceptives, and estrogen replacement therapy that result in lower levels and reduced exposure to gonadotropins. In the current study, bovine OSE cells were used as a model system for normal OSE cells. Both FSH and hCG (an LH agonist) stimulated (³H)thymidine incorporation in OSE cells. Results were confirmed using recombinant FSH and hCG. Gonadotropins stimulated growth of one ovarian cancer cell line (OCC1) but not another (SKOV3). Additional experiments examined growth factor expression by OSE cells. Gonadotropins stimulated steady state levels of three growth factors, KGF, HGF and KL in OSE cells. These growth factors have also been shown to stimulate OSE growth. Therefore, gonadotropins may stimulate OSE growth directly or indirectly through stimulation of growth factor expression. The ability of gonadotropins to stimulate OSE cells is proposed to be important in the development and progression of ovarian cancer. Small microtumors have been proposed to be stimulated to grow and progress under conditions with elevated gonadotropins. Treatments such as estrogen replacement therapy in high risk women may help reduce exposure to gonadotropins and reduce the risk of development of active ovarian cancer disease.

    This abstract is being presented on Tuesday, August 3 at 8:00 AM to 10:15 AM at CUB 2nd Floor Ballroom.