Under normal circumstances, a pulse of GnRH is transmitted through the hypothalamic-hypophyseal portal circulation to the anterior pituitary, where, having interacted with its appropriate receptor, the hormone stimulated the release of a pulse of LH and perhaps FSH. Thus, whereas the frequency of gonadotropin pulses appear to reflect the frequency with which the GnRH pulse generator discharges its peptide, gonadotropin pulse amplitude may represent the combined effects of the amount of GnRH reaching the gonadotrophs and the prevailing state of responsivity of the gonadotropin secreting cells. The latter response characteristics are determined both by information encoded within the neural signal and by the gonadal hormone milieu. Failure of the hypothalamic GnRH neuronal system to generate an appropriate neural signal or of the pituitary gonadotrophs to perceive, transduce, and respond to the neural signal may result in a spectrum of disorders ranging from a mild compromise of reproductive function to infertility.
Initiation of the pulsatile pattern of gonadotropin secretion occurs just before puberty with nighttime increases in LH. After puberty, pulsatile secretion is maintained throughout the 24-hour period, but it varies in both amplitude and frequency. In puberty, arcuate activity begins with a low frequency of GnRH release and proceeds through a cycle of acceleration of frequency, characterized by passage from total inactivity, to nocturnal activation, to the full adult pattern. The progressive changes in FSH and LH reflect this activation of GnRH pulsatile secretion.
Normal menstrual cycles require the maintenance of the pulsatile release of GnRH within a critical range of frequency and amplitude. This pulsatile release is mediated by a catecholaminergic mechanism and can be modified by gonadal steroids and a variety of brain peptides.
THE HYPOTHALAMUS AND GnRH SECRETION.
Within the hypothalamus are peptidergic neural cells that secrete the releasing and inhibiting hormones.
