Synergistic effects of steroids with FSH on folliculogenesis, steroidogenesis and FSH- and hCG-receptors in hypophysectomized mice

Abstract

Injection of ovine FSH (4 micrograms day-1) for 4 days into hypophysectomized mice does not restore folliculogenesis to normal cyclic values. This may be due to insufficient production of oestradiol. The present study was designed to determine whether FSH- and LH-induced oestradiol was critical for growth and differentiation of follicles at all stages. Twelve days after hypophysectomy, mice were injected s.c. with 10, 50 or 250 micrograms oestradiol cyclopentylpropionate daily with or without ovine FSH (4 micrograms day-1) for 1-4 days. One ovary from each animal was used for histology. From the second ovary, follicles were isolated at different stages and incubated with [3H]thymidine for 3 h to determine the rate of DNA synthesis. Incubation medium and serum were used for steroid determinations. After oestradiol treatment alone, there was a dose-dependent response in serum oestradiol, but ovarian and uterine weights did not increase further with the increasing doses of oestradiol administered. This finding was consistent with an increase in the number of preantral follicles and small antral follicles but excluding the development of preovulatory follicles. Treatment with 10 and 50 micrograms of oestradiol cyclopentylpropionate did not prevent antral follicles from undergoing atresia. The higher dose (250 micrograms day-1) of oestradiol cyclopentylpropionate delayed atresia of antral follicles and maintained more large healthy antral follicles. After concurrent injection of oestradiol and FSH, ovarian weight was 2-3 times greater than with either FSH or oestradiol alone; the number of follicles and follicular DNA synthesis at all stages of development increased without any signs of atresia; the in vitro accumulation of oestradiol also increased. Oestradiol alone induced FSH receptors in granulosa cells, but did not induce hCG receptors in any ovarian compartment; FSH alone induced FSH and hCG receptors in granulosa cells but not in thecal-interstitial tissues, whereas, oestradiol plus FSH enhanced FSH receptors in granulosa cells and LH/hCG receptors in granulosa and thecal-interstitial tissues. The synergistic effect of oestradiol with FSH was mimicked by the same dose of diethylstilboestrol, testosterone or dihydrotestosterone, but the latter steroids increased only the number of antral follicles, presumably because of their shorter half-lives. These results indicate that in mice oestradiol stimulates the growth of preantral and antral follicles and delays follicular atresia; oestrogens and androgens act synergistically with FSH to enhance follicular proliferation and differentiation, and prevent follicles from undergoing atresia.