IGF-1 Influences Gonadotropin-Releasing Hormone Regulation of Puberty

The pubertal process is initiated as a result of complex neuroendocrine interactions within the preoptic and hypothalamic regions of the brain. These interactions ultimately result in a timely increase in the secretion of gonadotropin-releasing hormone (GnRH). Researchers for years have believed that this increase is due to a diminished inhibitory tone which has applied a prepubertal brake on GnRH secretion, as well as to the gradual development of excitatory inputs driving the increased release of the peptide. Over the years, insulin-like growth factor-1 (IGF-1) has emerged as a prime candidate for playing an important role in the onset of puberty. This review will first present initial research demonstrating that IGF-1 increases in circulation as puberty approaches, is able to induce the release of prepubertal GnRH, and can advance the timing of puberty. More recent findings depict an early action of IGF-1 to activate a pathway that releases the inhibitory brake on prepubertal GnRH secretion provided by dynorphin, as well as demonstrating that IGF-1 can also act later in the process to regulate the synthesis and release of kisspeptin, a potent stimulator of GnRH at puberty.