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 (∆LH) and induced follicle-stimulating hormone (∆FSH) and compared with spontaneous fluctuations in gonadotropins [spontaneous luteinizing hormone (∆_■LH) and spontaneous follicle-stimulating hormone (∆_■FSH)). One to four low-dose (0.0125 or 0.025 μg/kg IV) pulses of GnRH were given every 2 hr between 0800 and 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 μg/ kg dose) and 218 ± 33 pg/ml (0.025 μg/kg dose). In early pubertal children,the maximal ALH was similar to or less than the maximal nocturnal A.LH (maximum, ALH 7.0 ± 0.2 versus maximum A.LH ± 1.3 mlU/ml in boys, 7.0 ± 1.2 versus 16.0 ± 3.0 mlU/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 ∆FSH and ∆_■FSH were similar in three prepubertal female patients (3.0 ± 0.2 versus 2.8 ± 0.2 mlU/ml). AFSH was greater than A.FSH 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 suggest that the amplitude of nocturnal GnRH pulses is equal to or greater than that previously reported in normal men. Speculation: Direct measurement of hypophysial portal plasma concentrations of GnRH in human beings is impractical. Nevertheless, detailed comparison of spontaneous fluctuations in plasma follicle- stimulating and luteinizing hormones with gonadotropin responses induced by a known concentration of exogenous gonadotropin- releasing hormone (GnRH) should provide reasonable estimates of GnRH pulse amplitude. The current studies suggest that: (1) in early pubertal children, the amplitude of nocturnal GnRH pulses equals or exceeds that of normal men; (2) the initial nocturnal rise in plasma LH characteristically noted in early pubertal boys is the result of a transient increase in the frequency of GnRH secretion; and (3) if GnRH is secreted episodically before puberty, GnRH pulse amplitude is low.