Catecholestrogens inhibit proliferation and DNA synthesis of porcine granulosa cells in vitro: comparison with estradiol, 5 alpha-dihydrotestosterone, gonadotropins and catecholamines.

Studies were conducted to assess the role of catecholestrogens on ovarian follicular growth using cultured porcine granulosa cells. Effects of the catecholestrogens, 2-hydroxyestradiol (2-OH-E2) and 2-methoxyestradiol (2-MeO-E2) were compared to those of estradiol (E2). Treatment with saturating concentrations of 2-OH-E2 caused a significantly greater decrease in cell numbers measured after 2 days of treatment than E2 treatment. The inhibitory effect of 2-OH-E2 was time and concentration dependent, not associated with a change in the viability of cells, and was partially reversible. The potency of 2-MeO-E2 to inhibit cell numbers was similar to or greater than that of 2-OH-E2. 2-MeO-E2 had a greater inhibitory effect on DNA synthesis, as measured by [3H]thymidine incorporation into trichloroacetic acid-precipitable macromolecules, than 2-OH-E2 or E2 in the absence or presence of insulin, epidermal growth factor or platelet-derived growth factor. Concurrent treatment with epinephrine significantly enhanced the inhibitory effect of 2-OH-E2 on granulosa cell DNA synthesis. Collectively, these studies indicate that catecholestrogens are more potent inhibitors of granulosa cell replication than E2 and 5 alpha-dihydrotestosterone (DHT), and that catecholamines may modulate the antimitotic activity of 2-OH-E2. These results support the hypothesis that catecholestrogens play a role in proliferation of granulosa cells during growth of ovarian follicles.