A non-neuronal cholinergic system of the ovarian follicle
A non-neuronal cholinergic system of the ovarian follicle
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DOI：
10.1016/j.aanat.2005.06.005
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发表时间：
2005-11-01
影响因子：
2.2
通讯作者：
Kunz, L
中科院分区：
文献类型：
--
作者：
Mayerhofer, A;Kunz, L
我们最近提供的证据表明，乙酰胆碱（ACh）是一种非神经元性的卵巢内信号分子，由颗粒细胞（GCs）产生，似乎在卵泡生长中起信号因子的作用。乙酰胆碱-乙酰转移酶（choline-acetyltransferase, ChAT）仅在啮齿类动物和灵长类动物的生长卵泡中表达。卵泡期的限制取决于促卵泡激素（FSH）的活性，这可能表明乙酰胆碱可能是一种尚不清楚的促卵泡激素作用的局部介质。在乙酰胆碱作用方面，我们正在进行的研究表明，它们可能通过GCs中不同的毒蕈碱乙酰胆碱受体（MR）发挥作用，也可能在卵母细胞中以重叠的方式发挥作用。为了阐明功能细节，我们研究了从排卵前卵泡中分离的培养人GCs。MRs的激活增加细胞内钙，例如，诱导主转录因子egr-1，这意味着参与细胞分化事件。乙酰胆碱激动剂还激活钙活化钾通道（BKCa），导致膜超极化，从而激活其他电压依赖性离子通道。这些事件链的实验调节导致甾体生成改变，这意味着乙酰胆碱在内分泌功能中的关键作用。进一步的乙酰胆碱作用包括间隙连接分子连接蛋白43的磷酸化和GCs之间细胞间通讯的破坏。这可能允许强偶联的GCs从卵泡的功能合胞体中逃逸，以启动增殖。用胆碱能剂处理后，培养的人GCs的增殖确实明显增加。ACh/MR的作用还远未被充分认识，可能包括健康生长卵泡的表观遗传调控。尽管卵巢胆碱能系统的许多方面，包括，例如，卵泡乙酰胆碱对携带mr的卵母细胞的影响，仍有待研究。目前的数据表明乙酰胆碱是一种新兴的、独特的卵巢内信号分子。(c) 2005 Elsevier GmbH版权所有。
We have recently provided evidence that acetylcholine (ACh) is a non-neuronal intraovarian signalling molecule, produced by granulosa cells (GCs) and which appears to act as signalling factor in the growing follicle. The ACh biosynthesis enzyme, choline-acetyltransferase (ChAT), is expressed only in growing, antral follicles in rodent and primate species. This restriction to follicle stages, which depend on the activity of follicle-stimulating hormone (FSH), may suggest that ACh could be an as yet unknown local mediator of FSH actions. In respect of ACh actions, our ongoing studies indicate that they may be exerted via different muscarinic ACh-receptors (MR) in GCs, but also in oocytes in an overlapping fashion. To elucidate functional details we have studied cultured human GCs isolated from preovulatory follicles. Activation of MRs increases intracellular calcium and, e.g., induces the master transcription factor egr-1, implying involvement in cell differentiation events. ACh agonists also activate a calcium-activated potassium channel (BKCa) resulting in membrane hyperpolarization, which allows activation of other voltage-dependent ion channels. Experimental modulation of the chain of these events causes altered steroidogenesis, implying a crucial role of ACh in endocrine functions. Further ACh actions include phosphorylation of the gap junction molecule connexin 43 and disruption of intercellular communication between GCs. This may allow strongly coupled GCs to escape from the functional syncytium of the follicle in order to initiate proliferation. Proliferation is indeed strongly increased in cultured human GCs when treated with cholinergic agents. The repertoire of ACh/MR actions is far from being fully appreciated and may include epigenetic regulation in healthy growing follicles. Although many aspects of the ovarian cholinergic system, including, for instance, influence of follicular ACh on the MR-bearing oocyte, remain to be examined. The present data pinpoint ACh as an emerging, unique intraovarian signalling molecule. (c) 2005 Elsevier GmbH. All rights reserved.