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The GnRH Pulse Generator

المؤلف:  Wass, J. A. H., Arlt, W., & Semple, R. K. (Eds.).

المصدر:  Oxford Textbook of Endocrinology and Diabetes

الجزء والصفحة:  3rd edition , p1252-1253

2026-10-17

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The fundamental nature of pulsatile GnRH secretion— including the neuroanatomical components of the GnRH pulse generator and mechanisms underlying episodic GnRH release— remains un clear. The mediobasal hypothalamus, which contains both the in fundibular (arcuate) nucleus and the median eminence, appears to contain all requisite components of the GnRH pulse generator. In monkeys and sheep, LH pulse initiation is temporally associated with discrete episodes of neuronal firing (multiple unit electrical activity) in the area of the mediobasal hypothalamus (Figure 1); and in monkeys, experimental electrical stimulation of the mediobasal hypothalamus provokes GnRH release into the hypo physeal portal system. Moreover, pulsatile LH secretion is maintained in monkeys after mediobasal hypothalamic isolation from the remainder of the brain; and isolated human mediobasal hypothalami release GnRH in a pulsatile fashion.

Fig1. Temporal relationship between hypothalamic multiple unit activity (MUA) and pulses of luteinizing hormone (LH) in the peripheral circulation. These data were obtained from an ovariectomized monkey. Adapted with permission from Knobil E. The electrophysiology of the GnRH pulse generator in the rhesus monkey. J Steroid Biochem 1989; 33:669– 71. Copyright © 1989 Elsevier Ltd. (21).

Numerous studies suggest that pulsatility is an intrinsic property of GnRH neurons; and coordination of GnRH release may reflect extensive interconnections among GnRH neurons. However, a number of observations suggest that kisspeptin, NKB, and dynorphin help to orchestrate coordinated GnRH neuronal activity. Although mechanisms remain unclear, some investigators have proposed a model whereby initial NKB release stimulates kisspeptin secretion, which initiates a GnRH pulse; and subsequent dynorphin release inhibits kisspeptin secretion, terminating the GnRH pulse. Although pulsatile GnRH release may occur in the absence of kisspeptin action (e.g. humans with KISSR mutations demonstrate low- amplitude LH pulses), it seems clear that kisspeptin is mandatory for normal GnRH secretion.