Suter K J, Pohl C R, Plant T M
Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pennyslvania 15261, USA.
Endocrinology. 1998 Jun;139(6):2774-83. doi: 10.1210/endo.139.6.6055.
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.
本研究的目的是确定雄性恒河猴青春期时脉冲式促性腺激素释放激素(GnRH)释放的开环增强模式和节奏。通过静脉间歇性输注合成肽进行预处理,原位垂体对GnRH的反应性先增强后维持,以此为指标,将原位垂体间歇性促黄体生成素(LH)分泌作为GnRH释放的指标。10只雄性猴子在12至20个月大时被阉割,植入留置静脉导管,并饲养在专门的笼子里,允许在最小程度的限制下远程接入静脉循环,且不干扰明暗周期。通过在GnRH预处理暂时中断的情况下,每隔12分钟测量一次循环LH浓度的瞬间变化,持续7小时,来评估内源性GnRH释放。每当通过脉冲检测程序识别出LH分泌脉冲时,就推断有GnRH释放。最早在14个月大时开始检查夜间脉冲式GnRH释放(1900 - 0200时)。在20个月大之前,每隔40天评估一次GnRH释放,此后尽可能每隔10天评估一次。开发了一种简单的算法来确定对促性腺激素细胞的促垂体驱动发育性增加的年龄。这被称为零日,被认为代表开始GnRH释放青春期模式的年龄。在确定青春期GnRH释放开始后,交替进行夜间和白天(1100 - 1800时)的GnRH评估。在零日(在24至29个月大时观察到)之前,观察到GnRH释放呈稳定、低频(<1次脉冲/7小时)、低振幅模式。青春期前GnRH脉冲发生器活动模式的终止表现为夜间相对迅速地转变为强劲的高频活动模式。在一些动物中,仅在30天的时间段内就实现了夜间GnRH脉冲频率加速至成年频率(6 - 7次脉冲/7小时)。尽管夜间GnRH脉冲发生器活动青春期加速的开始似乎与GnRH脉冲幅度的增加有关,但无法解读该参数随后的发育变化。在一些动物中,青春期加速开始后GnRH释放的脉冲模式被活动减少的时期打断,这似乎与垂体 - 肾上腺轴的状态无关。这些发现表明,导致青春期前GnRH释放减少模式终止从而启动青春期隐匿过程的神经生物学机制,有可能以惊人的快速时间进程展开。在去性腺情况下,脉冲式GnRH释放青春期加速的内在节奏在完整猴子中受睾丸反馈抑制的程度仍有待确定。