The impact of the GH-IGF-I axis on gonadotropin secretion: inferences from animal models.

Given the tight, temporal coupling between growth and reproductive development, the idea that a common signal may regulate both adolescent growth and the initiation of puberty has been the focus of much research. Since the rate-limiting step for the onset of puberty is the appropriate hypothalamic secretion of gonadotropin-releasing hormone (GnRH), any factor important for the initiation of puberty must affect GnRH pulsatility. This review examines the hypothesis that GH and/or IGF-I are growth-related signals that regulate the release of GnRH, initiating puberty. By extension, this review also addresses the hypothesis that the GH axis also impacts GnRH and gonadotropin secretion in post-pubertal individuals and, thus, affects the maintenance of fertility in adults. The review examines data from a range of animal models employing a number of different strategies which directly manipulate the activity of either GH or IGF-I. The success of these strategies for producing the desired effects on the GH-IGF-I axis is somewhat variable. Although IGF-I may only play a permissive role in the maintenance of adult fertility, acting at the level of the gonad to increase sensitivity to gonadotropin stimulation, the data indicate that IGF-I is essential for reproductive maturation. However, in addition to its well-documented effects on the gonad, the specific mode of action of IGF-I on the neuroendocrine hypothalamus and GnRH pulsatility remains to be determined. Available evidence suggests that such action by IGF-I may be mediated through neurotransmitter effects on GnRH neurons, changing the availability of metabolic substrates for neuronal activity, or remodeling of synaptic input into GnRH neurons.