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.
Spicer
L J
LJ
Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Hammond
J M
JM
D000077584:2-Methoxyestradiol; D000818:Animals; D002395:Catecholamines / Q000494:pharmacology; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D002393:Estrogens, Catechol / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000502:physiology; D006062:Gonadotropins / Q000494:pharmacology; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D013552:Swine
D002395:Catecholamines; D002393:Estrogens, Catechol; D006062:Gonadotropins; D013196:Dihydrotestosterone; D004958:Estradiol; D000077584:2-Methoxyestradiol; D005640:Follicle Stimulating Hormone; D004247:DNA; C001390:2-hydroxyestradiol