Divergent roles of growth factors in the GnRH regulation of puberty in mice
Sara A. DiVall, … , Sally Radovick, Andrew Wolfe
Sara A. DiVall, … , Sally Radovick, Andrew Wolfe
Published July 12, 2010
Citation Information: J Clin Invest. 2010;120(8):2900-2909. https://doi.org/10.1172/JCI41069.
View: Text | PDF
Research Article Endocrinology

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

Sara A. DiVall, Tameeka R. Williams, Sarah E. Carver, Linda Koch, Jens C. Brüning, C. Ronald Kahn, Fredric Wondisford, Sally Radovick, Andrew Wolfe

×

Figure 7

Developmental differences in GnRH neuronal morphology are present in GnRH-IGFRKO mice.

Options: View larger image (or click on image) Download as PowerPoint
Developmental differences in GnRH neuronal morphology are present in GnR...
Forty-micrometer sections of hypothalami from control mice or GnRH-IGFRKO were stained for GnRH immunoreactivity. (A) Graph of the number of GnRH neurons counted in control (n = 6) versus GnRH-IGFRKO (n = 6) adult mice. OVLT is labeled as 0. Each interval graphed encompasses 160 μm, thus 4 successive slices. Images (original magnification, ×100) show an area 640 mm rostral to OVLT (B), the OVLT (C), and an area 640 mm caudal to OVLT (D) in control and GnRH-IGFRKO (E–G) mice. Scale bars: 100 μm. Dendritic structure of individual GnRH neurons was determined in P10 (H), P26 (I), and adult (J) mice. n = 3 mice for each postnatal day and genotype. The irregularity of individual GnRH neurons was determined in P10 (K), P26 (L), and adult (M) mice. n = 3 mice of each postnatal day and genotype. Values are mean ± SEM. *P < 0.05, **P < 0.01.