clock time

FIGURE 15 Plasma LH and testosterone measured every 20 minutes reveal nocturnal pulsatile secretion of GnRH in a pubertal 14-year-old boy. (From Boyer RM, Rosenfeld RS, Kapen S et al., J Clin Invest 1974; 54:609. With permission.)

gonadotropins increase after gonadectomy in prepuber-tal subjects and fall with gonadal hormone administration. The system is extremely sensitive to feedback inhibition during this time, but suppression of the pulse generator cannot be explained simply as a change in the set point for feedback inhibition. The plasma concentration of gonadotropins is high in juvenile subjects whose testes have failed to develop and who consequently lack testosterone, but rise even higher when these subjects reach the age when puberty would normally occur. Thus, restraint of the GnRH pulse generator imposed by the central nervous system diminishes at the onset of puberty.

Early stages of puberty are characterized by the appearance of high-amplitude pulses of LH during sleep (Fig. 15). Testosterone concentrations in plasma follow the gonadotropins, and there is a distinct day/ night pattern. As puberty progresses, high-amplitude pulses are distributed throughout the day at the adult frequency of about one every 2 hours. Sensitivity of the pituitary gland to GnRH increases during puberty, possibly as a result of a self-priming effect of GnRH on gonadotropes. GnRH increases the amount of releasable FSH and LH in the gonadotropes and may also increase the number of its receptors on the gonadotrope surface. The underlying neural mechanisms for suppression of the GnRH pulse generator in the juvenile period are not understood. Increased inhibitory input from neuropep-tide Y (NPY)- and y-aminobutyric acid (GABA)-secret-ing neurons has been observed, but neither the factors that produce nor terminate such input are understood. Clearly, the onset of reproductive capacity is influenced by, and must be coordinated with, metabolic factors and attainment of physical size. In this regard, as we have seen (Chapter 44) puberty is intimately related to growth. Onset of puberty, especially in girls, has long been associated with adequacy of body fat stores, and it appears that adequate circulating concentrations of leptin (Chapter 43) are permissive for the onset of puberty, but available evidence indicates that leptin is not the trigger. It is likely that some confluence of genetic, developmental, and nutritional factors signals readiness for reproductive development and function.

Suggested Readings

Crowley WF, Jr, Filicori M, Spratt DI, Santoro NF. The physiology of gonadotropin-releasing hormone (GnRH) in men and women. Rec Prog Horm Res 1985; 41:473-526.

Crowley WF, Jr, Whitcomb RW, Jameson JL, Weiss J, Finkelstein JS, O'Dea LSL. Neuroendocrine control of human reproduction in the male. Recent Prog Horm Res 1991; 47:349-387.

George FW, Wilson JD. Hormonal control of sexual development. Vitamins Horm 1986; 43:145-196.

Hayes FJ, Hall JE, Boepple PA, Crowley WF, Jr. Clinical review 96—differential control of gonadotropin secretion in the human: endocrine role of inhibin. J Clin Endocrinol Metab 1998; 83: 1835-1841.

Huhtaniemi I. Mutations of gonadotrophin and gonadotrophin receptor genes: what do they teach us about reproductive physiology? J ReprodFertil 2000; 119:173-186.

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