Use of granulosa-luteal cell culture to evaluate low and high clinical responses to menotropin stimulation.
The cause of a poor response to human menopausal gonadotropin (hMG) remains unexplained. To determine whether aromatase activity of cultured granulosa cells obtained from relatively low estradiol (E2) responders (serum E2 < 1000 pg/ml) to hMG therapy differed from that of good responders (E2 > or = 1000 pg/ml), we prospectively compared serum E2 on the day of human chorionic gonadotropin administration to in vitro aromatase activity following a 72-h culture. Granulosa cells were obtained from seven women undergoing hMG therapy and oocyte aspiration. Follicle stimulating hormone (FSH) was added to one-half of the cultures. Serum E2 was determined by radioimmunoassay, and aromatase activity was determined indirectly by measuring tritiated water formed by aromatization of 1-beta [3H] androstenedione to estrogen in 1 h. In this study, luteinized granulosa cells from patients with a relatively low serum E2 produced less estrogen in cultures when compared to cells from higher responders (p < 0.01). Aromatase activity was not significantly increased by FSH in the relatively high responders, whereas FSH stimulated a significant increase in aromatase activity in cells from lower responders (p < 0.001). Our results indicate that the clinical response to hMG is at least partly due to the "quality" of granulosa cell aromatase activity. A clinically relevant "block" to FSH action may be present in vivo in low responders which can be reversed in culture by addition of FSH.
Hurst
B S
BS
Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore.
Zacur
H A
HA
Schlaff
W D
WD
Berkovitz
G D
GD
D001141:Aromatase / Q000378:metabolism; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000627:therapeutic use; D004958:Estradiol / Q000097:blood / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006107:Granulosa Cells / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008184:Luteal Cells / Q000187:drug effects* / Q000201:enzymology; D008596:Menotropins / Q000494:pharmacology*; D011446:Prospective Studies
D006063:Chorionic Gonadotropin; D004958:Estradiol; D008596:Menotropins; D005640:Follicle Stimulating Hormone; D001141:Aromatase