REGULATION OF INSULIN-LIKE GROWTH-FACTOR-I AND PROGESTERONE SYNTHESIS BY INSULIN AND GROWTH-HORMONE IN THE OVINE OVARY

Insulin-like growth factor-I(IGF-I) is an intraovarian regulator of follicular development in the rat, but it is uncertain how applicable this model is to other species. Ovine granulosa and luteal cells were cultured for 2 wk in defined medium to investigate the regulation of ovarian IGF-I synthesis. IGF-I was measured by RIA of concentrated media extract, and progesterone production was also assessed. In granulosa cell cultures from preovulatory follicles, IGF-I output was initially undetectable with the output rising from about Day 6, whereas midcycle luteal cells produced low concentrations of IGF-I throughout the culture period. In granulosa cells, insulin in the range 0.1-10 mu g/ml stimulated a dose-dependent increase in output per day of IGF-I and also caused IGF-I production to start at an earlier time in culture, but a lower dosage (10 ng/ml) consistently increased progesterone synthesis. High dosages of estradiol (10(-6) M) caused a small increase in IGF-I production whereas lower dosages had no effect. Growth hormone (GH) alone (10 ng/ml-10 mu g/ml) did not stimulate either progesterone or IGF-I output. In the presence of insulin, GH caused a marked increase in progesterone but had no effect on IGF-I, These results suggest that IGF-I is not a major product of granulosa cells in the ewe, although there is low luteal production. Furthermore they indicate that the actions of the metabolic hormones insulin and GH on ovarian progesterone synthesis are probably mediated directly through their own receptors rather than through either ovarian IGF-I synthesis or the type 1 IGF receptor.