Central Insulin-Like Growth Factor 1 Receptors Play Distinct Roles in the Control of Reproduction, Food Intake, and Body Weight in Female Rats1

Abstract

Estradiol and progesterone induction of the LH surge in ovariectomized female rats requires concurrent activation of brain insulin-like growth factor 1 (IGF1) receptors. The present study determined whether brain IGF1 receptor signaling is required for estrous cyclicity in gonadally intact female rats. A selective IGF1 receptor antagonist (JB-1) or vehicle was continuously administered into the third ventricle by osmotic minipumps. Following surgical placement of the minipumps, all rats temporarily reduced food intake, lost weight, and suspended estrous cycles. Control rats resumed cycles within a few days and exhibited compensatory hyperphagia until they returned to presurgical body weight. Animals receiving JB-1 had severely delayed or absent estrous cycles, failed to show rebound feeding, and regained body weight more slowly. Vehicle-infused animals pair fed to JB-1-treated rats had even lower body weights but resumed estrous cycles sooner than those given drug alone. Chronic infusion of IGF1 alone had no effect on any of these parameters, but coinfusion of IGF1 with the antagonist completely reversed JB-1 effects on food intake and estrous cyclicity and partially reversed the effects on body weight. There were no significant differences in the expression of galanin-like peptide (Galp) or Kiss1 mRNA in the arcuate or periventricular hypothalamic area of control and JB-1-treated animals at a time point when food intake and estrous cycles were different between controls and JB-1-treated rats. These data suggest that brain IGF1 signaling is necessary for normal estrous cycles as well as compensatory hyperphagia and that IGF1 modulation of the reproductive axis is not secondary to reduced food intake.

Divergent roles of growth factors in the GnRH regulation of puberty in mice

“…Intracerebroventricular infusion of an IGF-1R antagonist to adult rats results in loss of estrous cyclicity not observed in rats administered vehicle (39). Estrous cyclicity is restored with coinfusion of IGF-1 and the receptor antagonist.…”

PDK-1/FoxO1 pathway in POMC neurons regulatesPomcexpression and food intake

“…Therefore, even if insulin signaling was defective, PDK-1 activation occurred by activation of leptin signaling. Alternatively, a receptor other than Ir, for example insulin-like growth factor-1 receptor (Igf1r), in POMC neurons can compensate for inactivation through Ir (35). Similarly, insulin receptor substrates (Irs) other than Irs2 in POMC neurons can compensate for Irs2 action (7, 39).…”

Insulin-like growth factor I and its binding protein-3 are regulators of lactation and maternal responsiveness

“…IGF-1 signalling in the brain supports neuronal survival and neuroprotection during the development of the CNS and in adults following brain injuries 30 . In the hypothalamus, IGF-I can feedback to the growth hormone axis but may also affect reproductive neuroendocrine functions 31–33 . However, the effects of IGF-I on lactation and prolactin release, an important aspect of reproduction, have not been investigated.…”