RECOMBINANT HUMAN FOLLICLE-STIMULATING-HORMONE STIMULATES MULTIPLE FOLLICULAR-GROWTH, BUT MINIMAL ESTROGEN PRODUCTION IN GONADOTROPIN-RELEASING-HORMONE ANTAGONIST-TREATED MONKEYS - EXAMINING THE ROLE OF LUTEINIZING-HORMONE IN FOLLICULAR DEVELOPMENT AND STEROIDOGENESIS

The two-cell theory predicts that follicular steroidogenesis requires the coordinate actions of both FSH and LH; however, the role of LH in follicular growth is less clear. The present study was designed to inv estigate the relative importance of LH and FSH in follicular growth an d steroidogenesis. Cynomolgus monkeys were treated with a GnRH antagon ist (antide; 3 mg/kg.day) for 20 days beginning in the midluteal phase of the menstrual cycle. After 10 days of antide administration, monke ys were injected with recombinant human FSH (rhFSH; 10 IU; n = 3), hum an menopausal gonadotropin (hMG; 10 IU; n = 3), or FSH plus 0.5 IU LH (n = 3) twice daily for 10 days. rhFSH stimulated multiple follicular development; however, peak serum estradiol levels were only 943 +/- 19 5 pmol/L. In contrast, monkeys treated with the same dose of hMG had s ignificantly higher (P < 0.05) peak estradiol levels (6013 +/- 1322 pm ol/L). The addition of 0.5 IU LH to the rhFSH treatment resulted in se rum estradiol levels similar to those in monkeys treated with rhFSH on ly. Importantly, no differences in follicle number or size were eviden t among these treatment groups. Follicular fluid estradiol levels were consistent with serum levels (rhFSH, 187 +/- 11 nmol/L; hMG, 1531 +/- 173 nmol/L). Even larger proportional differences in follicular fluid androstenedione (rhFSH 13.6 +/- 1.4 nmol/L; hMG, 307 +/- 97.7 nmol/L) levels were found. The results in this LH-deficient primate model sug gest that FSH alone is capable of stimulating ovarian follicular growt h; however, the resulting follicles manifest minimal estradiol product ion, probably due to deficiencies in the LH-induced precursors to estr adiol.