Effects of insulin-like growth factor I and interactions with transforming growth factor α and LH on proliferation of chicken granulosa cells and production of progesterone in culture

The effects of insulin-like growth factor I (IGF-I), alone, and in combination with LH or transforming growth factor alpha (TGF-alpha), on replication and progesterone production by cultured avian granulosa cells obtained from the three largest (F1-F3) follicles were studied. IGF-I and TGF-alpha stimulated proliferation of granulosa cells in a dose-dependent manner, and responsiveness decreased as the cells matured. IGF-I stimulated progesterone production from granulosa cells of all the follicles with no change in ED50 value during follicular maturation; however, the maximum response was from cells derived from F1 follicles. IGF-I plus LH had an additive effect on progesterone production by cells from all follicles. In contrast, TGF-alpha inhibited basal and LH- and IGF-I-stimulated progesterone production. These data show that IGF-I and TGF-alpha may interact with each other during granulosa cell maturation, such that efficacy of IGF-I increases, while that of TGF-alpha decreases before ovulation. Furthermore, both growth factors interact with LH, either to enhance or inhibit progesterone production by granulosa cells. However, LH, IGF-I and TGF-alpha combine to stimulate proliferation of granulosa cells.