Interactions of insulin-like growth factor-I, insulin and estradiol with GnRH-stimulated luteinizing hormone release from female rat gonadotrophs

Background: It is well established that ovarian steroids modulate gonadotro pin secretion from anterior pituitary cells. It has been speculated that in sulin and IGF-I might influence gonadotropin secretion. Objective: To investigate the effects of IGF-I and estradiol alone, or comb inations of IGF-I with insulin and estradiol on GnRH-stimulated LH release from female rat pituitary cells in serum-supplemented and serum-free cultur e conditions. Methods: Pituitary cells were incubated For 24 h or 48 h with a series of i ncreasing concentrations of IGF-I or estradiol and stimulated with 1 nmol/l GnRH for 3 h, To determine the interaction of IGF-I and estradiol on GnRH- stimulated LH secretion, cells were exposed to increasing concentrations of ICF-I and 100 pmol/l estradiol for 24 h. We also investigated the effects of combined treatment with IGF-I and insulin on GnRH-stimulated LH secretio n. Results: Our findings indicate that long-term IGF-I treatment (24 h) alone has a significant augmenting effect on GnRH-stimulated LH release in serum- free medium only, with a maximum at low concentrations (10 and 100 pmol/l). Estradiol significantly increased GnRH-induced LH release in a dose-depend ent manner. The extent of GnRH-stimulated LEI secretion by long-term estrad iol treatment (24 h) was significantly greater in serum-supplemented (+42%) medium than in serum-free medium. Estradiol facilitated IGF-I-primed LH re sponses to GnRH in serum-free medium. In contrast, in serum-supplemented me dium, the facilitating potential of estradiol was lower. We also found that , in GnRH-stimulated cells, LH release was augmented by insulin treatment, in contrast to quiescent cells that had been pretreated with Inn pmol/l IGF -I alone and 1 nmol/l insulin alone. Conclusions: IGF-I and to a lesser extent insulin stimulate GnRH-induced LH secretion from pituitary gonadotrophs. This action is enhanced by estradio l treatment of the cells. However, the well known stimulatory action of est radiol on LH secretion is dependent on the presence of growth factors.