Marshall J C, Dalkin A C, Haisenleder D J, Griffin M L, Kelch R P
Department of Internal Medicine, University of Virginia, Charlottesville.
Trans Am Clin Climatol Assoc. 1993;104:31-46.
The data reviewed in this chapter provide evidence that the pattern of GnRH secretion appears to be an important factor in regulating gonadotropin subunit gene expression, gonadotropin synthesis and hormone secretion. The data on gonadotropin synthesis were obtained in rodents and hence, must be interpreted with caution when applied to primates. Despite this reservation, the data suggest a similarity of regulatory mechanisms in mammalian species. The data also provide an explanation for the mechanisms whereby a single gonadotropin-releasing hormone can differentially regulate the three gonadotropin genes and allow differential hormone secretion. In overall agreement with this view, the observations during pubertal maturation reveal increasing GnRH pulsatile secretion during puberty with an evolution from predominant FSH to a predominant LH secretion by the gonadotropes. In males, the patterns of GnRH secretion appear to be fairly consistent throughout adult life, but in women cyclic changes occur which perhaps are important in maintaining cyclic ovulation. It is proposed that once pubertal maturation has been established, GnRH is secreted at a relatively fast frequency (one pulse per hour), and an essential feature of repeated ovulatory cycles is the slowing of this GnRH stimulus during the luteal phase: to allow subsequent preferential FSH release. This slowing of GnRH secretion appears to be effected by estradiol and progesterone acting to enhance hypothalamic opioid activity. Similar mechanisms involving increased opioid tone appear to be causally related to the reduced frequency and irregular GnRH stimulus seen in hypothalamic amenorrhea and hyperprolactinemia. In contrast, some forms of polycystic ovarian disease may reflect abnormalities of the estradiol-progesterone/opioid/GnRH neuron feedback mechanisms, with failure to establish slowing in the peripubertal anovulatory cycles. The resulting persistent GnRH stimulus increases LH with consequent effects of abnormal follicular maturation and enhanced ovarian androgen production. Present data are supportive of these hypotheses, but future studies will determine whether these views prove to be correct. However, current data provide strong support for the view that the pattern of GnRH secretion is a critical factor in the regulation of differential gonadotropin synthesis and secretion in mammalian species.
本章回顾的数据表明，促性腺激素释放激素（GnRH）的分泌模式似乎是调节促性腺激素亚基基因表达、促性腺激素合成及激素分泌的一个重要因素。关于促性腺激素合成的数据是在啮齿动物中获得的，因此应用于灵长类动物时必须谨慎解读。尽管有这一保留意见，但这些数据表明哺乳动物物种的调节机制具有相似性。这些数据还解释了单一促性腺激素释放激素能够差异性调节三个促性腺激素基因并实现不同激素分泌的机制。总体而言，与这一观点一致的是，青春期成熟过程中的观察结果显示，青春期GnRH脉冲式分泌增加，促性腺激素细胞分泌从以促卵泡生成素（FSH）为主逐渐演变为以促黄体生成素（LH）为主。在男性中，GnRH分泌模式在成年期似乎相当一致，但在女性中会出现周期性变化，这可能对维持周期性排卵很重要。有人提出，一旦青春期成熟确立，GnRH会以相对较快的频率分泌（每小时一次脉冲），而反复排卵周期的一个基本特征是黄体期这种GnRH刺激减缓：以便随后优先释放FSH。GnRH分泌的这种减缓似乎是由雌二醇和孕酮作用增强下丘脑阿片样物质活性所导致的。涉及阿片样物质张力增加的类似机制似乎与下丘脑性闭经和高催乳素血症中GnRH刺激频率降低和不规律有关。相反，某些形式的多囊卵巢疾病可能反映了雌二醇 - 孕酮/阿片样物质/GnRH神经元反馈机制的异常，在青春期前无排卵周期中未能出现减缓。由此产生的持续GnRH刺激会增加LH，进而导致卵泡异常成熟并增强卵巢雄激素生成。目前的数据支持这些假设，但未来的研究将确定这些观点是否正确。然而，当前数据有力支持了这样一种观点，即GnRH分泌模式是调节哺乳动物物种中促性腺激素差异性合成和分泌的关键因素。
