Estimation of GnRH Pulse Amplitude during Pubertal Development

Abstract

SummaryFourteen children between 2.5 and 16 years of age were studied to provide a quantitative estimate of the changes in gonadotropinreleasing hormone (GnRH) pulse amplitude in hypophysial portal plasma during puberty. Responses to physiologic doses of synthetic GnRH were measured [induced luteinizing hormone (ALH) and induced follicle-stimulating hormone (AFSH)] and compared with spontaneous fluctuations in gonadotropins [spontaneous luteinizing hormone (A.LH) and spontaneous follicle-stimulating hormone (A.FSH)I. One to four lowdose (0.0125 or 0.025 &kg IV) pulses of GnRH were given every 2 hr between OSOO and 1600 or 2200 and 0400 hr. Maximal peripheral plasma concentrations of GnRH one min after pulses averaged 107 f 25 pg/ml (S.E.) (0.0125 pg/ kg dose) and 218 * 33 pg/ml (0.025 &kg dose). In early pubertal children,the maximal ALH was similar to or less than the maximal nocturnal L L H (maximum, ALH 7.0 f 0.2 versus maximum A.LH 7.0 * 1.3 mIU/ml in boys, 7.0 f 1.2 versus 16.0 f 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 AFSH and L F S H that luteinizing hormone (LH), but not follicle-stimulating hormone (FSH) release increases strikingly at puberty in both sexes, whereas FSH release is greater in prepubertal girls than boys.Information about GnRH secretion into the hypophysial portal system has been obtained via direct measurement in several animal species (1,3,6,18,22). Camel et al. (3) have measured portal blood GnRH in monkeys and found it to vary between 10 to 800 pg/ml. In humans, suchmeasurements are impractical, and information has been obtained via indirect techniques. We have pre-viously used responses to synthetic GnRH to istimate the hypophysial portal plasma concentration of GnRH in men and to gain information about its secretory pattern. On the basis of these studies, we concluded that the portal plasma concentration of GnRH varied between <30 and 300 pg/ml (a), an estimate similar to those obtained by direct measurement in animals. A similar study in prepubertal children would be difficult to interpret because of the shallow dose response curve for LH in these children (7,9). In this study, we have utilized the striking FSH responses of prepubertal and hypogonadal children, as well as the marked day/night difference in LH secretion characteristic of early puberty to estimate GnRH pulse amplitude. MATERIALS AND METHODSwere similar in three prepubertal female patients (3.0 * 0.2 versus 2.8 * 0.2 mIU/ml). AFSH was greater than L F S H in two patients All studies were done in the Clinical Research Center after with gonadal dysgenesis (bone ages, 2.5 m d 5 years) m d in one written informed parental These studies were approved by the Human Investigation Committee of t...

Pulsatile Secretion of LH and FSH in Prepubertal and Early Pubertal Boys Revealed by Ultrasensitive Time-Resolved Immunofluorometric Assays

“…Thus the onset of puberty may be associated with an increase in GnRH secretion rather than an increase in sensitivity of the pituitary gonadotroph to GnRH. This agrees with the observation of Corley et al (1) whose indirect estimations of GnRH pulse amplitudes in the hypophysial portal circulation of prepubertal and early pubertal children showed an increase in amplitude at the onset of puberty.…”

“…With our method we could observe much lower plasma LH levels than previously reported for prepubertal boys (1,4,5). In boys less than 9 y old the levels ranged from 0.02 to 0.8 IU/L (mean 0.1 IU/L).…”

“…The increase is apparently due to increased pulse frequency and amplitude. In pubertal children and adults LH, and presumably GnRH are secreted episodically (1)(2)(3). However, some controversy still exists about the pulsatile secretKn of LH in prepubertal children (4)(5)(6)(7)(8)(9)(10).…”

Problems in the Use of Pulsatile Gonadotrophin-Releasing Hormone for the Induction of Puberty

“…We propose that GnRH pulse ampli tude at initiation of therapy should be low, contrary to the findings of Corley et al [17] and treatment given at night only in the first instance. As puberty advances, the amplitude of GnRH pulses should be increased and treatment given during the day as well as by night.…”

Selective inhibition of follicle-stimulating hormone secretion by estradiol. Mechanism for modulation of gonadotropin responses to low dose pulses of gonadotropin-releasing hormone.

“…The individual hormone concentrations are shown for patient 14 in Fig. 5, and mean data for patients [14][15][16][17][18] are shown in Fig. 6.…”