TRANSIENT INDUCTION OF POLYCYSTIC OVARY-LIKE SYNDROME IN IMMATURE HYPOTHYROID RATS

Hypothyroidism in the human female is often associated with ovarian fo llicular cysts and hyperandrogenism, two cardinal signs of polycystic ovary syndrome. To explore the intraovarian changes that lead to folli cular cyst formation in hypothyroidism, we have created a prepubertal hypothyroid rat model. These hypothyroid rats are hyperandrogenic and develop transient ovarian follicular cysts. Hypothyroidism in newborn rats was induced by providing the lactating dams with 0.04% propylthio uracil (PTU)-containing water. Subsequently, female rats were weaned a nd kept on PTU-containing water. On Day 25 of age, the rats were prime d with 15 international units of pregnant mare's serum gonadotropin (P MSG) in 100 mu l of phosphate buffered saline. Two days later, to init iate pseudopregnancy, they were injected with five international units of human chorionic gonadotropin (hCG), The animals were sacrificed at appropriate times, and blood and ovaries were collected for analyses. Control experiments were done with euthyroid rats. Two days after PMS G injection, well-developed antral follicles were observed in both the hypothyroid and euthyroid rats. Two days after hCG injection, while t he euthyroid rat ovaries, as expected, contained numerous corpora lute a (CL), the hypothyroid rat ovaries still retained antral follicles, S ome of these follicles with degenerating oocytes showed signs of lutei nization, By 3-4 days post-hCG injection, the hypothyroid rat ovaries developed cystic follicles, By Day 6, however, the hypothyroid rat ova ries were indistinguishable from those of the euthyroid rats. Although serum testosterone concentrations were significantly elevated in the hypothyroid rats on Days 1-3, progesterone concentrations were not sig nificantly different from the euthyroid animals. However, by Days 8-14 , the hypothyroid rats had significantly higher serum progesterone con centrations. This model will be useful for investigating the intraovar ian biochemical changes that lead to follicular cyst development in re sponse to acute gonadotropin treatment.