SYNERGISTIC EFFECTS OF STEROIDS WITH FSH ON FOLLICULOGENESIS, STEROIDOGENESIS AND FSH-RECEPTORS AND HCG-RECEPTORS IN HYPOPHYSECTOMIZED MICE

Injection of ovine FSH (4 mu g day(-1) for 4 days into hypophysectomiz ed mice does not restore folliculogenesis to normal cyclic values. Thi s may be due to insufficient production of oestradiol. The present stu dy was designed to determine whether FSH- and LH-induced oestradiol wa s critical for growth and differentiation of follicles at all stages. Twelve days after hypophysectomy, mice were injected s.c. with 10, 50 or 250 mu g oestradiol cyclopentylpropionate daily with or without ovi ne FSH (4 mu g day(-1)) for 1-4 days. One ovary from each animal was u sed for histology. From the second ovary, follicles were isolated at d ifferent stages and incubated with [H-3]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 w eights did not increase further with the increasing doses of oestradio l administered. This finding was consistent with an increase in the nu mber of preantral follicles and small antral follicles but excluding t he development of preovulatory follicles. Treatment with 10 and 50 mu g of oestradiol cyclopentylpropionate did not prevent antral follicles from undergoing atresia. The higher dose (250 mu g day(-1)) of oestra diol cyclopentylpropionate delayed atresia of antral follicles and mai ntained more large healthy antral follicles. After concurrent injectio n of oestradiol and FSH, ovarian weight was 2-3 times greater than wit h either FSH or oestradiol alone; the number of follicles and follicul ar DNA synthesis at all stages of development increased without any si gns of atresia; the in vitro accumulation of oestradiol also increased . Oestradiol alone induced FSH receptors in granulosa cells, but did n ot induce hCG receptors in any ovarian compartment; FSH alone induced FSH and hCG receptors in granulosa cells but not in thecalinterstitial tissues, whereas, oestradiol plus FSH enhanced FSH receptors in granu losa cells curd LH/hCG receptors in granulosa and thecalinterstitial t issues. The synergistic effect of oestradiol with FSH was mimicked by the same dose of diethylstilboestrol, testosterone or dihydrotestoster one, but the latter steroids increased only the number of antral folli cles, presumably because of their shorter half-lifes. These results in dicate that in mice oestradiol stimulates the growth of preantral and antral follicles and delays follicular atresia; oestrogens and androge ns act synergistically with FSH to enhance follicular proliferation an d differentiation, and prevent follicles from undergoing atresia.