Sisk C L, Richardson H N, Chappell P E, Levine J E
Neuroscience Program and Department of Psychology, Michigan State University, East Lansing, Michigan 48824, USA.
Endocrinology. 2001 Jul;142(7):2929-36. doi: 10.1210/endo.142.7.8239.
Pubertal development in female rats is characterized by increased LH levels and the appearance of estrogen-dependent afternoon LH mini-surges. In these studies we performed the first analysis of GnRH patterns in peripubertal rats to determine whether there are similar changes in pulsatile GnRH release. Microdialysis samples were collected at 5-min intervals throughout a 5-h afternoon period from 22 rats sampled on a single day between 30-47 days of age. Adult female rats were sampled on proestrus for comparison. In 30- to 33-day-old rats, GnRH release was infrequent (2.7 pulses/5 h; n = 3), whereas intermediate pulse frequencies were observed in 34- to 37-day-old rats (6.4 pulses/5 h; n = 9) and 38- to 42-day-old (5.0 pulses/5 h; n = 5) rats. The highest GnRH pulse frequencies were observed in 43- to 47-day-old rats (9.4 pulses/5 h; n = 5). Mean GnRH pulse amplitude did not vary significantly with age. Animals sampled before vaginal opening (VO) exhibited significantly slower GnRH pulse frequencies than those sampled after vaginal opening (1.3 pulses/5 h pre-VO vs. 7.6 pulses/5 h post-VO; P = 0.01). An afternoon increase in GnRH secretion, defined operationally as a greater than 25% increase in mean GnRH levels in the last half of the sampling period and tentatively termed a mini-surge, was observed in 0%, 33%, 40%, and 60% of 30- to 33-, 34- to 37-, 38- to 42-, and 43- to 47-day-old rats, respectively. An overall increase in GnRH pulse frequency was observed in females displaying a mini-surge (9.0 pulses/5 h with mini-surge compared with 4.7 pulses/5 h with no mini-surge). The mini-surge itself, however, was associated with a late afternoon increase in GnRH pulse amplitude and not in pulse frequency. In adult proestrous rats, peak levels during the GnRH surge were an order of magnitude greater than those reached in pubertal animals. Our findings demonstrate that pubertal maturation in the female rat is associated with an acceleration of GnRH pulse generator activity and that later stages of pubertal maturation are characterized by the appearance of afternoon increases in GnRH release that may underlie previously reported mini-surges in LH.
雌性大鼠的青春期发育特征为促黄体生成素(LH)水平升高以及出现依赖雌激素的下午LH小幅激增。在这些研究中,我们首次分析了青春期前后大鼠的促性腺激素释放激素(GnRH)模式,以确定GnRH脉冲式释放是否存在类似变化。在下午5小时期间,每隔5分钟从22只30至47日龄单日采样的大鼠中采集微透析样本。成年雌性大鼠在动情前期采样用于比较。在30至33日龄的大鼠中,GnRH释放不频繁(2.7次脉冲/5小时;n = 3),而在34至37日龄的大鼠(6.4次脉冲/5小时;n = 9)和38至42日龄(5.0次脉冲/5小时;n = 5)的大鼠中观察到中等脉冲频率。在43至47日龄的大鼠中观察到最高的GnRH脉冲频率(9.4次脉冲/5小时;n = 5)。平均GnRH脉冲幅度并未随年龄显著变化。在阴道开口(VO)前采样的动物,其GnRH脉冲频率显著低于阴道开口后采样的动物(VO前为1.3次脉冲/5小时,VO后为7.6次脉冲/5小时;P = 0.01)。在30至33日龄、34至37日龄、38至42日龄和43至47日龄的大鼠中,分别有0%、33%、40%和60%观察到下午GnRH分泌增加,在操作上定义为采样期后半段平均GnRH水平增加超过25%,并初步称为小幅激增。在出现小幅激增的雌性大鼠中观察到GnRH脉冲频率总体增加(有小幅激增时为9.0次脉冲/5小时,无小幅激增时为4.7次脉冲/5小时)。然而,小幅激增本身与下午晚些时候GnRH脉冲幅度增加有关,而与脉冲频率无关。在成年动情前期大鼠中,GnRH激增期间的峰值水平比青春期动物达到的水平高一个数量级。我们的研究结果表明,雌性大鼠的青春期成熟与GnRH脉冲发生器活动加速有关,并且青春期成熟的后期阶段特征为下午GnRH释放增加,这可能是先前报道的LH小幅激增的基础。