New concepts of the neuroendocrine regulation of gonadotropin surges in rats
New concepts of the neuroendocrine regulation of gonadotropin surges in rats
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DOI：
10.1095/biolreprod56.2.293
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发表时间：
1997-02-01
影响因子：
3.6
通讯作者：
Levine, JE
中科院分区：
文献类型：
--
作者：
Levine, JE
在自发排卵的物种中，两个关键事件介导排卵前促性腺激素激增的刺激：1）排卵前LHRH激增的神经分泌和2）脑垂体对LHRH神经分泌触发的反应性急剧增加。反过来，这些过程依赖于排卵前雌激素分泌的正反馈作用和启动激增的特定神经信号。在雌性大鼠中，浪涌的神经信号主要来自24小时神经钟，从而限制了浪涌的时间到发情前期的下午。然而，目前尚不清楚神经信号如何与特定脑细胞中的内分泌信号（雌激素）汇合，以及它们的细胞整合如何导致促性腺激素激增的适当分泌。先前的研究表明，雌激素可能通过打开神经“门”发挥其促进作用，从而允许将日常神经信号传递到引发浪涌的神经元群。雌激素如何使神经通路通畅？传统观点认为，类固醇激素可以通过调节神经递质受体表达、细胞内第二信使产生和蛋白激酶活性对信号传导功效施加容许效应。然而，最近的证据表明，雌激素也可能有能力允许神经递质信号通路和平行的转录调控通路之间的串扰。孕激素受体是一种雌激素诱导的转录因子，它在与腺苷酸环化酶刺激偶联的神经递质受体刺激后被反式激活，即使在没有其同源配体的情况下。因此，刺激促性腺激素激增的神经和内分泌信号的会聚可能发生在孕激素受体的水平上：雌激素可能刺激孕激素受体的表达，而孕激素受体又可能最初被突触信号反式激活。活化的孕酮受体可随后调节靶基因的转录，所述靶基因控制在支配LHRH基因表达和/或脉动LHRH释放的神经回路中的递质合成和释放。类似的机制可能在垂体促性腺激素细胞中起作用，其中孕酮受体的配体非依赖性反式激活介导神经分泌和雌激素正反馈信号的整合，导致垂体对LHRH的反应性增加。有人提出，“播种”的特定的神经元群和垂体促性腺激素与孕激素受体，也许其他诱导转录因子，包括雌激素的允许作用的刺激促性腺激素激增的重要基础。这种综合模型的有效性仍有待证实，因为它可能在其他物种中产生促性腺激素激增的重要性。
In species that ovulate spontaneously, two key events mediate the stimulation of preovulatory gonadotropin surges: 1) neurosecretion of a preovulatory LHRH surge and 2) an acute increase in responsiveness of the pituitary gland to the LHRH neurosecretory trigger. These processes, in turn, depend upon both the positive feedback actions of preovulatory estrogen secretions and specific neural signals for initiation of the surge. In female rats, the neural signals for the surge are principally derived from the 24-h neural clock, thereby limiting the timing of surges to the afternoon of proestrus. It remains unclear, however, how neural signals converge with endocrine signals (estrogen) in specific brain cells and how their cellular integration leads to appropriate secretion of gonadotropin surges. previous work has suggested that estrogen may exert its facilitatory actions by opening a neural ''gate,'' thereby allowing transmission of the daily neural signal to surge-initiating neuronal groups. How may estrogen act to render a neural pathway patent? A conventional view holds that steroid hormones can exert permissive effects on signaling efficacy by modulating neurotransmitter receptor expression, intracellular second messenger production, and protein kinase activity. However, recent evidence has suggested that estrogen may also have the capacity to permit cross-talk between neurotransmitter signaling pathways and parallel transcriptional regulatory pathways. The progesterone receptor is an estrogen-inducible transcription factor that has been shown to be transactivated-even in the absence of its cognate ligand-after stimulation of neurotransmitter receptors coupled to adenylate cyclase stimulation. Thus, the convergence of neural and endocrine signals for the stimulation of gonadotropin surges could occur at the level of the progesterone receptor: estrogen may stimulate expression of progesterone receptors, which in turn may be initially transactivated by synaptic signals. Activated progesterone receptors may thereafter regulate transcription of target genes that control transmitter synthesis and release in neural circuitries governing LHRH gene expression and/or pulsatile LHRH release. An analogous mechanism may operate in pituitary gonadotrophs, in which ligand-independent transactivation of progesterone receptors mediates integration of neurosecretory and estrogen positive feedback signals, leading to increased pituitary responsiveness to LHRH. It is proposed that the ''seeding'' of specific neuronal groups and pituitary gonadotrophs with progesterone receptors, and perhaps other inducible transcription factors, comprises an important basis of estrogen's permissive role in the stimulation of gonadotropin surges. The validity of this integrative model remains to be confirmed, as does its possible importance in generating gonadotropin surges in other species.