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

Departments of Neuroscience,³ Obstetrics & Gynecology,⁴ Medicine,⁵ and Psychiatry & Behavioral Sciences,⁶ Albert Einstein College of Medicine, Bronx, New York 10461 Biology Department,⁷ Hope College, Holland, Michigan 49422

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.

brain, estrous cyclicity, feeding, hypothalamus, insulin-like growth factor receptor, luteinizing hormone, neuroendocrinology

¹Supported by NIH grants T32 DK07513 (B.J.T.), R01 HD29856 (A.M.E.), DK066238 (G.S.F.), R01DK066618 (G.J.S.), and the Skirball Foundation (A.M.E. and G.J.S.).

Correspondence: ²Brigitte J. Todd, Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Ave., F113, Bronx, NY 10461. FAX: 718 430 8654; e-mail: btodd{at}aecom.yu.edu

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				L. M. Garcia-Segura, B. Lorenz, and L. L DonCarlos The role of glia in the hypothalamus: implications for gonadal steroid feedback and reproductive neuroendocrine output Reproduction, April 1, 2008; 135(4): 419 - 429. [Abstract] [Full Text] [PDF]