Developmental Changes in Hypothalamic Insulin-Like Growth Factor-1: Relationship to Gonadotropin-Releasing Hormone Neurons

Reproductive development in vertebrates is controlled by changes in hypothalamic GnRH neurons and their inputs from other neurons and glia. One factor involved in the regulation of the GnRH system is the neurotrophic factor, IGF-1. To better understand the regulation of GnRH neurons by hypothalamic IGF-1, we quantified levels of IGF-1 mRNA in hypothalamic and preoptic regions containing GnRH cells, studied the effects of IGF-1 on GnRH gene expression, and examined the neuroanatomical relationship between GnRH neurons and hypothalamic IGF-1 in neonatal, peripubertal, and reproductively mature mice. Our results indicated that IGF-1 mRNA levels in the preoptic area and anterior hypothalamus peaked at postnatal day (P) 5, decreased through P20, and then increased through peripubertal and adult development. Second, IGF-1 had stimulatory effects on GnRH gene expression in explanted preoptic area-anterior hypothalamuses of P5 and peripubertal mice, with results varying by sex and duration of treatment. In contrast, IGF-1 had no effect or even inhibited GnRH gene expression in adult P60 mice. Third, GnRH perikarya coexpressed IGF-1, and this increased throughout sexual maturation. Taken together, the results suggest that IGF-1 can modulate GnRH neurons, that the sensitivity of GnRH neurons to IGF-1 changes developmentally, and that GnRH cells coexpress IGF-1.