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

Abstract

Background: It is well established that ovarian steroids modulate gonadotropin secretion from anterior pituitary cells. It has been speculated that insulin and IGF-I might influence gonadotropin secretion. Objective: To investigate the effects of IGF-I and estradiol alone, or combinations of IGF-I with insulin and estradiol on GnRH-stimulated LH release from female rat pituitary cells in serum-supplemented and serum-free culture conditions. Methods: Pituitary cells were incubated for 24 h or 48 h with a series of increasing 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 IGF-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 secretion. 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-dependent manner. The extent of GnRH-stimulated LH secretion by long-term estradiol treatment (24 h) was significantly greater in serum-supplemented (+42%) medium than in serumfree medium. Estradiol facilitated IGF-I-primed LH responses to GnRH in serum-free medium. In contrast, in serum-supplemented medium, 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 100 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 estradiol treatment of the cells. However, the well known stimulatory action of estradiol on LH secretion is dependent on the presence of growth factors.

The Luteinizing Hormone-releasing Hormone Inhibits the Anti-apoptotic Activity of Insulin-like Growth Factor-1 in Pituitary αT3 Cells by Protein Kinase Cα-mediated Negative Regulation of Akt

“…The IGF-1R is expressed in rat and mouse pituitary glands, and IGF-1 has been shown to stimulate the proliferation of pituitary cells (24). In addition, IGF-1 leads to an increase in basal and LHRH-stimulated release of LH from rat anterior pituitary explants and dispersed cells in vitro (36,37,58,59). IGF-1 increases FSH content and LHRH-stimulated FSH release in Coho salmon pituitary cells in vitro (60).…”

“…Like LHRH-I, IGF-1 treatment increases LH secretion by male rat pituitary cells (36). Moreover, IGF-1 enhances the LH response to LHRH-I in pituitary cells from male rats (37), pigs (38), fish (39), and sheep (40). IGF-1 also regulates growth in pituitary gonadotrope cells (41).…”

Insulin augments GnRH-stimulated LHβ gene expression by Egr-1

“…Insulin receptors are expressed in the rat anterior pituitary (Werther et al, 1987;Havrankova and Roth, 1978). Insulin augments GnRH-stimulated secretion of LH from anterior pituitary cells (Soldani et al, 1994;Xia et al, 2001). Neuron-specific disruption of the insulin receptor gene in mice (NIRKO mice) did not affect brain development but impaired fertility and decreased circulating levels of LH, mimicking hypogonadotropic hypogonadism (Bruning et al, 2000).…”

Molecular Regulation of Gonadotropin Secretion by Gonadotropin Releasing Hormone in Salmonid Fishes

“…For example, intraventricular administration of IGF-I in female rats increased plasma luteinizing hormone (LH) and advanced the onset of puberty (Hiney et al, 1996). The administration of IGF-I to rat pituitary cell cultures increased basal secretion of follicle-stimulating hormone (FSH) and LH and gonadotropin-releasing hormone (GnRH)-induced LH secretion (Kanematsu, et al, 1991;Soldani et al, 1994Soldani et al, , 1995Xia et al, 2001). Moreover, in male rats, IGF-I stimulated release of FSH and LH, with increased expression of the glycoprotein α (GPα) subunit gene but not of the FSHβ, nor LHβ subunit genes (Pazos et al, 2004).…”