The Pattern and Tempo of the Pubertal Reaugmentation of Open-Loop Pulsatile Gonadotropin-Releasing Hormone Release Assessed Indirectly in the Male Rhesus Monkey (Macaca mulatta)1

Abstract

The purpose of this study was to determine the pattern and tempo of the open-loop reaugmentation of pulsatile GnRH release at the time of puberty in the male rhesus monkey. Episodic LH secretion from the in situ pituitary, in which responsiveness to GnRH was first heightened and subsequently sustained by priming with an i.v. intermittent infusion of the synthetic peptide, was used as an index of GnRH discharges. Ten male monkeys were castrated between 12 and 20 months of age, implanted with indwelling venous catheters, and housed in specialized cages that permitted remote access to the venous circulation with minimal restraint and without interfering with the light-dark cycle. Endogenous GnRH release was assessed by examining moment-to-moment changes in circulating LH concentrations measured at 12-min intervals for 7 h while GnRH priming was temporarily interrupted. A discharge of GnRH was inferred whenever a pulse of LH secretion was identified by a pulse detection program. Examination of nocturnal pulsatile GnRH release (1900-0200 h) was initiated as early as 14 months of age. GnRH release was assessed at 40-day intervals before 20 months of age and at 10-day intervals whenever possible thereafter. A simple algorithm was developed to identify the age at which a developmental increase in hypophysiotropic drive to the gonadotroph occurred. This was termed day zero and was considered to represent the age at which a pubertal mode of GnRH release was initiated. After the initiation of pubertal GnRH release was established, alternate nighttime and daytime (1100-1800 h) assessments of GnRH were performed. Before day zero, which was observed between 24 and 29 months of age, a stable, low frequency (<1 pulse/7 h), low amplitude pattern of pulsatile GnRH release was observed. Termination of the prepubertal mode of GnRH pulse generator activity was manifest as a relatively rapid nocturnal shift to a robust high-frequency pattern of activity. In some animals, the nocturnal acceleration to an adult GnRH pulse frequency (6-7 pulses/7 h) was attained within an epoch of only 30 days. Although initiation of the pubertal acceleration in nocturnal GnRH pulse generator activity seemed to be associated with an increase in GnRH pulse amplitude, it was not possible to decipher the subsequent developmental changes in this parameter. In some animals, the pattern of pulsatile GnRH release after the initiation of the pubertal acceleration was punctuated by periods of diminished activity, which seemed to be unrelated to the state of the pituitary-adrenal axis. These findings demonstrate that the neurobiological mechanisms that lead to the termination of the prepubertal mode of diminished GnRH release, and that therefore initiate the insidious process of puberty, have the potential to unfold with a surprisingly rapid time course. The extent to which the intrinsic tempo of the pubertal acceleration of pulsatile GnRH release in the agonadal situation is dampened by testicular feedback in the intact monkey remains to be established.