IGF-1 Receptors in Leptin Responsive Neurons Control Body Weight, Growth and Pubertal Development

Presentation Number: OR40-1
Date of Presentation: April 4th, 2016

Mengjie Wang*1, Iyad Manaserh2 and Jennifer Wootton Hill3
1University of Toledo, Toledo, OH, 2University of Toledo Health Science campus, Toeldo, 3University of Toledo School of Medicine, Toledo, OH

Abstract

Growth and reproduction are tightly linked. Growth hormone deficiency results in a profound suppression of postnatal growth accompanied by delayed puberty (of a week or more in mice) and delayed reproductive senescence, while GH excess is correlated with the reverse (1). The specific mechanism underlying this delay is undefined. IGF-1 administration advances pubertal timing, however deletion of IGF-1R from GnRH neurons only delays puberty by 3-4 days (2). Thus, upstream, metabolically active neurons may play a role in the effects of IGF-1 on pubertal timing. Although neurons in the hypothalamus that express leptin receptors (LepRb) are known to modulate the timing of puberty, whether IGF-1 receptor (IGF-1R) signaling in these neurons controls pubertal development is unknown. To test whether IGF-1 action specifically in LepRb expressing cells affects pubertal development and fertility, we used Cre-loxp technology to generate transgenic mice lacking IGF-1R exclusively in LepRb expressing cells (termed IGF-1RLepRb). IGF-1RLepRb females experienced a delay in vaginal opening and in first estrus. IGF-1RLepRb females showed decreased body weight from week 2 to week 16 while IGF-1RLepRb males caught up with controls after week 6. Both IGF-1RLepRb females and males exhibited decreased body length. Decreased food intake, glucose intolerance and hyperinsulinemia were seen in IGF-1RLepRb males while IGF-1RLepRb females are comparable with controls. Both IGF-1RLepRb females and males showed less energy expenditure and physical activities. Our data identify a novel role for IGF-1R signaling in leptin responsive neurons in the control of energy balance and pubertal development.

 

Nothing to Disclose: MW, IM, JWH