Estimation of GnRH pulse amplitude during pubertal development

Fourteen children between 2.5 and 16 years of age were studied to provide a quantitative estimate of the changes in gonadotropin-releasing hormone (GnRH) pulse amplitude in hypophysial portal plasma during puberty. Responses to physiologic doses of synthetic GnRH were measured [induced luteinizing hormone (delta LH) and induced follicle-stimulating hormone (delta FHS)] and compared with spontaneous fluctuations in gonadotropins [spontaneous luteinizing hormone (delta sLH) and spontaneous follicle-stimulating hormone (delta FHS)]. One to four low-dose (0.0125 or 0.025 microgram/kg IV) pulses of GnRH were given every 2 hr between 0800 ad 1600 or 2200 and 0400 hr. Maximal peripheral plasma concentrations of GnRH one min after pulses averaged 107 +/- 25 pg/ml (S.E.) (0.0125 microgram/kg dose) and 218 +/- 33 pg/ml (0.025 microgram/kg dose). In early pubertal children the maximal delta LH was similar to or less than the maximal nocturnal delta sLH (maximum, delta LH 7.0 +/- 0.2 versus maximum delta sLH 7.0 +/- 1.3 mIU/ml in boys, 7.0 +/- 1.2 versus 16.0 +/- 3.0 mIU/ml in girls). Luteinizing hormone (LH) responses were low or undetectable in children whose bone ages were less than 10 years. When discernible, LH pulse frequency was similar during daytime and nighttime sampling periods in early pubertal boys. However, two hourly injections of GnRH given during the day did not simulate the initial nocturnal rise in LH. Overall mean delta FSH and delta sFSH were similar in three prepubertal female patients (3.0 +/- 0.2 versus 2.8 +/- 0.2 mIU/ml). delta FSH was greater than delta sFSH in two patients with gonadal dysgenesis (bone ages, 2.5 and 5 years) and in one prepubertal girl. The gonadotropin responses seen in early pubertal children suggests that the amplitude of nocturnal GnRH pulses is equal to or greater than that previously reported in normal men.