ABSTRACT
The existence of a hypothalamic pulse generator is well established, which triggers GnRH pulsatile secretion by hypothalamic neurons and activates gonadotropin secretion by the pituitary. However, the nature of this pulse generator and the detailed signaling mechanisms, setting the pubertal clock to trigger the onset of puberty at a certain predetermined time point, are largely unknown. Humans share the fundamental principles of the regulation of pubertal activation with other vertebrate animals including nonhuman primates, but the set of neuroendocrine mediators involved seem to differ between species. However, a common principle seems to be that the pulse generator is intrinsically active and must be reversibly suppressed by inhibitory signals from neurotransmitters such as GABA. In humans, the hypothalamic pulse generator is functional and shows sexual dimorphism already in the fetal stage. Postnatally it becomes more active during the first months of life in boys (“baby puberty”) and is then dampened to quiescence during childhood. At start of puberty, nightly reactivation of the GnRH pulse generator results in elevated levels of pulsatile LH secretion, triggering gonadal production and endocrine actions of the sex steroids. For reviews, see (1,2).
