EFFECTS OF RECOMBINANT HUMAN FOLLICLE-STIMULATING-HORMONE ON CULTURED HUMAN GRANULOSA-CELLS - COMPARISON WITH URINARY GONADOTROPINS AND ACTIONS IN PREOVULATORY FOLLICLES

The effects of recombinant human follicle stimulating hormone (rFSH; Org 32489) have been examined in human granulosa cells from ovaries obtained from women with spontaneous menses. In the first series of experiments the actions of rFSH on production of oestradiol and progesterone were compared with those of urinary-derived gonadotrophins. Recombinant FSH induced dose-dependent increases in production of both oestradiol and progesterone which were similar to the effects of 'pure' FSH (Metrodin(R)) and the International Standard IS 71/223. In further studies, the actions of rFSH on oestradiol production by individual preovulatory follicles were investigated; rFSH increased oestradiol accumulation from cells obtained from follicles before the luteinizing hormone (LH) surge. In contrast, rFSH inhibited oestradiol production by granulosa cells derived from a follicle after the onset of the LH surge, whereas the gonadotrophic action of growth hormone was maintained. Following preliminary reports of the in-vivo effects of rFSH in women, these findings provide further validation of the efficacy of rFSH in the human ovary. The results of studies of the preovulatory follicle illustrate the experimental importance of the availability of recombinant preparations of pure gonadotrophins, produced by recombinant technology, in the understanding of human ovarian function.