Sex steroids, growth hormone, insulin-like growth factor-1: neuroendocrine and metabolic regulation in puberty.

Abstract

The control of the onset of puberty involves the complex interaction of pituitary and gonadal hormones. At a preprogrammed time in a child's life there is an increase in the amplitude of GnRH pulses which triggers a cascade of events including increases in the amplitude of FSH and LH pulses, followed by marked increases in gonadal sex steroidal output, which in turn increases growth hormone (GH) and insulin-like growth factor-1 (IGF-1) production. Evidence suggests that there is an integral interaction between the endogenous opiate system and the hypothalamic-pituitary-gonadal axis, at least in the later stages of puberty in the male. Both androgenic and estrogenic hormones markedly increase GH production rates as measured by deconvolution models in the prepubertal human, and compelling data strongly suggest that it is indeed the estrogen which controls the feedback amplification of GH production during puberty even in the male. It appears that the prepubertal gonad is actively producing sex hormones which might be important in the control of GH production since early childhood. The translation of these neuroendocrine rhythms into distal metabolic actions is also reviewed. Utilizing isotopic tracer infusions of the essential amino acid leucine, studies clearly show a selective stimulation of whole body protein synthesis by both GH and IGF-1. GH, IGF-1 and androgenic hormones all increase in puberty, stimulating whole body protein anabolism during that period. However, we observed no protein-anabolic effect in the hypogonadal female given increasing doses of estrogen. The latter suggests that at least as it pertains to whole body protein effects, the action of androgens is probably mediated via the androgen and not the estrogen receptor, in clear distinction from the estrogen-mediated effects of androgens on the neuroendocrine axis. Calcium absorption and retention are also positively affected by the androgens as shown by significant increases in calcium absorption and retention after the administration of testosterone to the prepubertal male. This suggests an important role of sex steroidal hormones in the mineralization of the skeleton. GH, IGF-1 and sex steroids all markedly increase during puberty and their actions are amplified mutually as they control growth, increase muscle mass and affect the mineralization of the skeleton. The dichotomy of androgen and estrogen effects in the male and female may regulate the differential timing of the onset of puberty and final height in the two sexes. The synergistic actions of these anabolic hormones appear to be most significant during the finite years of puberty.