Gonadotropin-releasing hormone agonist suppression of ovarian tumorigenesis in mice of the Wx/Wv genotype.
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-Wx/Wv 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 Wx/Wv 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 Wx/Wv 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).
Department of Obstetrics and Gynecology, Rigshospitalet, Copenhagen, Denmark.
J
J
Blaakaer
M
M
Baeksted
S
S
Micic
P
P
Albrectsen
J
J
Rygaard
J
J
Bock
D000236:Adenoma / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D003692:Delayed-Action Preparations; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005838:Genotype; D017273:Goserelin / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control*; D010053:Ovary / Q000473:pathology; D014599:Uterus / Q000473:pathology
D003692:Delayed-Action Preparations; D017273:Goserelin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone