Interpulse interval of GnRH stimulation independently modulates LH secretion.

To examine the importance of the interpulse interval of gonadotropin-releasing hormone (GnRH) stimulation in modulating gonadotroph responsiveness, a fixed individualized dose of GnRH was administered to eight GnRH-deficient men at intervals selected randomly from the distribution of luteinizing hormone (LH) interpulse intervals of normal men. The responses were compared with data derived from a study of LH pulses in 20 normal men. A positive relationship was found between LH pulse amplitude and the preceding interpulse interval both in the GnRH-deficient (P less than 0.05) and in the normal (P less than 0.003) men. The distributions of LH pulse amplitudes appeared to differ between the two groups with failure of the study paradigm to reproduce the distribution of low-amplitude pulses of the normal men in the GnRH-deficient men. There was significantly more variability about the line that related interpulse interval and LH amplitude in the normal men (P less than 0.004) in whom the amount of GnRH could vary physiologically. This difference remained significant both for pulses with amplitudes below (P less than 0.01) or above (P less than 0.03) the mean of the normal men. These studies demonstrate that the GnRH interpulse interval is an independent determinant of pituitary responsiveness and that alterations in the amount of GnRH secreted from the hypothalamus are an important determinant of LH pulse amplitude in men.