To determine the regulatory mechanism of the LHRH release associated with puberty, episodic release of LHRH from the stalk-median eminence was measured using a push-pull perfusion technique in conscious prepubertal and peripubertal female monkeys. After insertion of a push-pull cannula into the stalk-median eminence, a modified Krebs-Ringer phosphate buffer solution was infused through the push-cannula, and perfusates were collected through the pull-cannula at 200 μl/10 min. LHRH in perfusates was determined by RIA. Two 6-h sampling sessions, in the morning (0600–1200 h; lights on 0600 h) and in the evening (1800–2400 h; lights off 1800 h) were performed in each animal. LHRH release patterns were analyzed in prepubertal (15.7 ± 0.7 months of age; mean ± SEM, n = 6) early pubertal (premenarcheal; 26.1 ±1.0 months, n = 7), and midpubertal (40.0 ±1.4 months, n = 6) monkeys.

Results were as follows: 1) LHRH release was pulsatile in all age groups. While LHRH release in five of six prepubertal animals consisted of small (amplitude < 2.5 pg/ml) pulses, in all peripubertal animals LHRH release was a mixture of small and large (amplitude > 2.5 pg/ml) pulses. 2) There was a significant developmental increase in mean LHRH release (P < 0.02), and this was particularly apparent in the evening. Mean LHRH release in the early and midpubertal groups was higher than that in the prepubertal group (P < 0.05 for morning and P < 0.01 for evening). The mean release in the evening of the midpubertal group further increased over that of the early pubertal group (P < 0.05). 3) Similarly, LHRH pulse amplitude increased developmentally (P < 0.01). Pulse amplitudes in early and midpubertal groups were higher than those in the prepubertal group (P < 0.05 for morning and P < 0.02 for evening). Again the amplitude in the evening further increased from the early pubertal to the midpubertal period (P < 0.05). 4) There was also a developmental increase in basal LHRH release (P < 0.01). The evening values in the early pubertal and midpubertal groups were higher than those in the prepubertal group (P < 0.05). 5) The interpulse interval decreased developmentally (P < 0.001). Interpulse intervals in early and midpubertal groups were shorter than those in the prepubertal group (P < 0.01 for morning and P < 0.025 for evening). However, the interpulse intervals of the midpubertal group were not different from those of early pubertal group. 6) In the midpubertal group evening values of both mean LHRH and amplitude were significantly higher (P < 0.01) than morning values. No circadian fluctuations were observed in the other two age groups.

These results suggest that 1) an increase in pulsatile LHRH release with a concomitant elevation in the pulse frequency and pulse amplitude occurred during the early pubertal stage before menarche; 2) LHRH output further increased with an elevation in only the pulse amplitude during the midpubertal stage; and 3) a nocturnal increase in LHRH output occurred during the midpubertal stage. Therefore, developmental changes in a regulatory mechanism resulting in the increased release of pulsatile LHRH may be a key factor responsible for the onset of puberty in female monkeys.