Gonadotropin-releasing hormone agonist suppression of ovarian tumorigenesis in mice of the W(x)/W(v) genotype

Abstract

Although many investigations have shown a correlation between elevated gonadotropin levels and ovarian tumors (the gonadotropin theory), the ovarian response to a specific suppression of the gonadotropins has not been elucidated. The ovaries of (C57BL/6J x C3H/HeJ) F1-W(x)/W(v) mice, which contain 1% of the normal oocyte count at birth, rapidly lose the follicular apparatus and develop a 100% incidence of bilateral complex tubular adenomas from the surface germinal epithelium, which is also the origin of 90% of human ovarian carcinomas. Plasma levels of LH and FSH are known to rise fourfold during the period of tumorigenesis. We compared tumor development in W(x)/W(v) mice after either injecting a GnRH agonist (3.6 mg slow-release goserelin depot, Zoladex Depot) or administering a sham injection every 28 days from the age of 7 days up to 245 days. All 15 W(x)/W(v) mice that received sham injections developed bilateral ovarian tubular adenomas from the surface germinal epithelium. In none of the 11 mice receiving the GnRH agonist was any tumor found (p < 0.00005), and a significant suppression of the gonadotropins was demonstrated (p < 0.00005).