Effect of thyroid hormone on CYP19 expression in ovarian granulosa cells from gonadotropin-treated immature rats

The present study was designed to determine the mechanisms by which serum estradiol levels are enhanced during gonadotropin-induced ovarian development in hypothyroid immature rats. Thyroidectomized (Tx)-immature rats receiving thyroidectomy on day 22 were treated with 8 IU equine chorionic gonadotropin (eCG) at 26 days of age to induce follicular development. in ovaries. Ovaries or ovarian granulosa cells were collected on the first proestrus (day 28). Enhanced expression of aromatase (CYP19) mRNA induced by eCG treatment was inhibited by injection of thyroxine (T-4: 5 mug x 6 times) in Tx rats. Ovarian granulosa cells harvested from Tx rats were cultured for 24 h in chemically defined serum-free medium containing gonadotropin in the presence of 3,5,3'-triidothyronine (T-3). Addition of low doses of T-3 (10(-8), 10(-7) M) to the medium significantly decreased 17beta-estradiol (E-2) levels, whereas high doses of T-3, (10(-6), 10(-5) M) did not inhibit the levels. Similar effects of T-3 on CYP19 mRNA expression were observed. These results indicate that augmentation of E-2 production in hypothyroid animals may be mediated, in part, via the stimulation of CYP19 mRNA expression in granulosa cells, which is suppressed by thyroid hormone.