Glucocorticoid influence on porcine granulosa cell IGF-I and steroid hormone production in vitro

The effect of cortisol on granulosa cell (GC) insulin-like growth factor I (IGF-I) synthesis, and IGF-mediated steroid production was examined at vari ous stages of follicle maturation. Granulosa cells were recovered from gilt s on Days 14, 18, and 20 of the estrous cycle, while luteinizing GC were re covered on Day 21, just prior to ovulation. The cells were cultured in seru m-free medium with increasing concentrations of cortisol (0, 1, 10, and 100 mu g/mL) for 5 d with or without IGF-I stimulation (10 ng/mL). During cult ure all cells were supplemented with FSH and androstenedione (A(4)) Cellula r IGF-I, progesterone (P-4) and estradiol-17 beta (E-2) production was dete rmined by specific radioimmunoassays (RIA), acid cell proliferation was ass essed. Granulosa cell IGF-I and steroid hormone synthesis increased (P<0.05 ) with follicle maturation. Direct exposure to high cortisol concentrations , however, altered both IGF-I synthesis and action. Cortisol treatment lowe red (P<0.05) IGF-I production by GC recovered on Days 18, 20, and 21. Furth ermore, it reduced (P<0.05) IGF-stimulated P-4 synthesis at all stages and decreased (P<0.05) IGF-stimulated E-2 synthesis by cells recovered on Day 1 4. In contrast, cortisol enhanced (P<0.05) FSH-stimulated P-4 production by GC collected on Days 14 and 18. The opposing effects on FSH and IGF-I acti on indicate that cortisol did not promote an overall suppressive effect on cell function, nor did it impair cell proliferation. Hence, these results d emonstrate that elevated cortisol concentrations can disrupt both IGF-I syn thesis and IGF-mediated actions by porcine GC under in vitro conditions, an d that specific disruptions are dependent on the stage of follicle maturati on. (C) 1999 by Elsevier Science Inc.