Effects of insulin-like growth factor I and insulin on proliferation and on basal and luteinizing hormone-induced steroidogenesis of bovine thecal cells: involvement of glucose and receptors for insulin-like growth factor I and luteinizing hormone.

Abstract

The objective of the present study was to determine the effects of IGF-I and insulin on cell proliferation, LH receptors, and basal and LH-induced progesterone and androstenedione production by bovine thecal cells. Cells from large (> or = 8mm) bovine follicles were cultured for 1 or 2 d in medium containing 10% fetal calf serum (FCS) and treated for 1 or 2 d in serum-free medium with IGF-I, insulin, and(or) LH. Treatment with 30 and 100 ng/mL of IGF-I for 1 or 2 d increased thecal cell numbers in the absence of LH regardless of whether treatments were initiated after 1 or 2 d of exposure to 10% FCS. Co-treatment with LH reduced the stimulatory effect of IGF-I on thecal cell numbers. Insulin at 10 and 100 ng/mL increased cell numbers in the presence of LH. Both IGF-I and insulin were ineffective at stimulating thecal cell progesterone or androstenedione production in the absence of LH. However, IGF-I and insulin increased (P < .05) androstenedione and progesterone production in the presence of LH. Alone, LH had little or no effect on androstenedione and progesterone production, whereas in the presence of 30 and 100 ng/mL IGF-I or 1 to 100 ng/mL insulin, LH stimulated (P < .05) androstenedione production. The stimulatory effects of IGF-I on cell proliferation and progesterone production were not detected in the presence of 100 ng/mL insulin. However, co-treatment with various doses of IGF-I and 100 ng/mL insulin further increased androstenedione production above that seen with insulin alone. In glucose-deficient medium, 25 to 75 mg/dL of glucose increased (P < .05) thecal cell proliferation, progesterone production, and androstenedione production. In the absence or presence of glucose, insulin (100 ng/mL) increased (P < .05) thecal cell proliferation, progesterone production, and androstenedione production. Treatment with 3, 10, or 100 ng/mL LH had no effect (P > .10) on the numbers of IGF-I binding sites on thecal cells but increased (P < .05) androstenedione production. Treatment with 10 and 100 ng/mL IGF-I increased (P <.01) numbers of LH/hCG binding sites. These results indicate that IGF-I and insulin may each play a significant role in thecal cell mitogenesis and LH-induced thecal cell steroidogenesis during follicular development in cattle and that glucose enhances these effects. Furthermore, the synergism between IGF-I and LH on increasing steroidogenesis does not seem to be mediated through increased binding sites for IGF-I in bovine thecal cells but rather, in part, through increased binding sites for LH.

Plasma urea nitrogen and progesterone concentrations and follicular dynamics in ewes fed proteins of different degradability

“…In addition, the higher intake of energy by ewes under overfeeding possibly caused increase in the blood glucose, insulin and IGF-I concentration. Insulin directly stimulates both mitosis and production of steroids in granulosa (Gutierrez et al, 1997) and theca (Stewart et al, 1995) cells, and IGF-I increases the sensitivity of cells to FSH (Adashi et al, 1985), promoting follicular development (Webb et al, 2004). Overfeeding can also increase the number of ovulations for resulting in higher hepatic metabolization of steroid hormones, consequently, decreasing the negative feedback of such hormones on the release of gonadotropins FSH and LH (Smith & Stewart, 1990).…”

Parturition to resumption of ovarian cyclicity: comparative aspects of beef and dairy cows

“…Role of insulin Insulin is primarily involved in glucose homeostasis but also serves as a metabolic signal influencing pituitary release of LH (Monget and Martin, 1997) and ovarian responsiveness to gonadotrophins (Stewart et al, 1995). Plasma insulin concentrations are influenced by both BCS and level of nutrition (Vizcarra et al, 1998), and may serve as a more sensitive indicator of nutritional status than BCS.…”

“…The inability to respond to increased LH pulse frequency may be owing to lack of granulosa cell LH receptors, which are known to be dependent on the combined actions of FSH and oestradiol 17β (Bao and Garverick, 1998). Follicular oestradiol-17β is, in turn, dependent on LH-stimulated production of androgens from the thecal cells that are dependent on peripheral concentrations of insulin and IGF-I (Stewart et al, 1995). Therefore, low plasma concentrations of insulin could reduce androgen and oestradiol production and thus compromise the ability of follicles to acquire LH receptors.…”

The roles of the insulin-like growth factor system and leptin as possible mediators of the effects of nutritional restriction on age at puberty and compensatory growth in dairy heifers

“…Yambayamba et al (1996) found that plasma glucose concentration in beef heifers was higher after restriction than during restriction; similar results were obtained in the present study. Glucose availability is also thought to be a metabolic signal involved with the control of GnRH secretion, and glucose availability has been shown to be associated with LH secretion in sheep (Bucholtz et al, 1996) and cattle (Stewart et al, 1995). Furthermore, Foster & Nagatani (1999) showed that the concentration of glucose increases during puberty.…”