title: Divergent roles of growth factors in the GnRH regulation of puberty in mice.
abstract: Pubertal onset, initiated by pulsatile gonadotropin-releasing hormone (GnRH), only occurs in a favorable, anabolic hormonal milieu. Anabolic factors that may signal nutritional status to the hypothalamus include the growth factors insulin and IGF-1. It is unclear which hypothalamic neuronal subpopulation these factors affect to ultimately regulate GnRH neuron function in puberty and reproduction. We examined the direct role of the GnRH neuron in growth factor regulation of reproduction using the Cre/lox system. Mice with the IR or IGF-1R deleted specifically in GnRH neurons were generated. Male and female mice with the IR deleted in GnRH neurons displayed normal pubertal timing and fertility, but male and female mice with the IGF-1R deleted in GnRH neurons experienced delayed pubertal development with normal fertility. With IGF-1 administration, puberty was advanced in control females, but not in females with the IGF-1R deleted in GnRH neurons, in control males, or in knockout males. These mice exhibited developmental differences in GnRH neuronal morphology but normal number and distribution of neurons. These studies define the role of IGF-1R signaling in the coordination of somatic development with reproductive maturation and provide insight into the mechanisms regulating pubertal timing in anabolic states.
authors.affiliation: Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland 21212, USA. sdivall1@jhmi.edu
authors.forename: Sara A
authors.initials: SA
authors.lastname: Divall
authors.forename: Tameeka R
authors.initials: TR
authors.lastname: Williams
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Carver
authors.forename: Linda
authors.initials: L
authors.lastname: Koch
authors.forename: Jens C
authors.initials: JC
authors.lastname: Brüning
authors.forename: C Ronald
authors.initials: CR
authors.lastname: Kahn
authors.forename: Fredric
authors.initials: F
authors.lastname: Wondisford
authors.forename: Sally
authors.initials: S
authors.lastname: Radovick
authors.forename: Andrew
authors.initials: A
authors.lastname: Wolfe
mesh_terms: D000818:Animals; D005260:Female; D005298:Fertility; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017526:Receptor, IGF Type 1 / Q000502:physiology*; D012741:Sexual Maturation; D015398:Signal Transduction
chemical_list: D007987:Gonadotropin-Releasing Hormone; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1