Loose M D, Terasawa E
Biol Reprod. 1985 Dec;33(5):1084-93. doi: 10.1095/biolreprod33.5.1084.
Previously we have hypothesized that an increase in luteinizing hormone-releasing hormone (LHRH) due to hypothalamic maturation is the key factor controlling the onset of puberty. This led to the working hypothesis that precocious puberty would be induced if LHRH is administered with an appropriate protocol. Thus, effects of pulsatile infusion of LHRH on the onset of first vaginal opening and first ovulation in immature female guinea pigs were studied. Luteinizing hormone-releasing hormone in hourly pulses of either 5 ng or 50 ng was infused through a chronically implanted jugular catheter for 9-29 days starting at 20 days of age. For the control experiment saline was infused in a similar manner. Infusion of 5 ng LHRH/h resulted in significantly earlier (P less than 0.001) ages at first vaginal opening (24.7 +/- 0.9 days) and at first ovulation (28.8 +/- 0.9 days) compared to saline controls (first vaginal opening 53.3 +/- 6.8 days; first ovulation 55.2 +/- 6.5 days). Infusion with a 10-fold higher LHRH dose (50 ng/h) also advanced the age at first vaginal opening (25.3 +/- 0.7 days), but precocious ovulation was no longer induced (53.7 +/- 5.3 days). Interestingly, LHRH infusion with the high dose resulted in a prolonged period of vaginal opening and cornification without ovulation. These results indicate that 1) pulsatile infusion of a small amount of LHRH with a constant frequency induces precocious puberty in a laboratory rodent, and 2) infusion of LHRH with a dose higher than the effective dose for the induction of early puberty results in a persistent estrous anovulatory syndrome. Therefore, the present study not only supports our hypothesis that an increase in endogenous LHRH release is responsible for the onset of puberty, but also further suggests that excessive release of LHRH or abnormal patterns of LHRH release may be involved in the etiology of the anovulatory persistent estrus syndrome.
此前我们曾提出假说，即下丘脑成熟导致促黄体生成激素释放激素（LHRH）增加是控制青春期启动的关键因素。由此得出一个工作假说：如果以适当的方案给予LHRH，将会诱发青春期早熟。因此，我们研究了LHRH脉冲式输注对未成熟雌性豚鼠首次阴道开口和首次排卵启动的影响。从20日龄开始，通过长期植入的颈静脉导管以每小时5 ng或50 ng的脉冲式输注促黄体生成激素释放激素，持续9至29天。作为对照实验，以类似方式输注生理盐水。与生理盐水对照组（首次阴道开口53.3±6.8天；首次排卵55.2±6.5天）相比，每小时输注5 ng LHRH导致首次阴道开口（24.7±0.9天）和首次排卵（28.8±0.9天）的年龄显著提前（P＜0.001）。输注10倍高剂量的LHRH（50 ng/h）也使首次阴道开口的年龄提前（25.3±0.7天），但不再诱发早熟排卵（53.7±5.3天）。有趣的是，高剂量LHRH输注导致阴道开口和角化期延长且无排卵。这些结果表明，1）以恒定频率脉冲式输注少量LHRH可在实验啮齿动物中诱发青春期早熟，2）输注高于诱导青春期早熟有效剂量的LHRH会导致持续性发情无排卵综合征。因此，本研究不仅支持了我们的假说，即内源性LHRH释放增加是青春期启动的原因，还进一步表明LHRH的过度释放或LHRH释放的异常模式可能与无排卵持续性发情综合征的病因有关。
