Gamma‐aminobutyric acid (GABA): a para‐ and/or autocrine hormone in the pituitary
Gamma‐aminobutyric acid (GABA): a para‐ and/or autocrine hormone in the pituitary
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DOI：
10.1096/fsb2fj000546fje
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发表时间：
2001-04
期刊：
影响因子：
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通讯作者：
A. Mayerhofer;B. Höhne-Zell;Katia Gamel-Didelon;Heike Jung†;P. Redecker;D. Grube;Henryk F. Urbanski§;Bruno Gasnier║;J. Fritschy;M. Gratzl
中科院分区：
文献类型：
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作者：
A. Mayerhofer;B. Höhne-Zell;Katia Gamel-Didelon;Heike Jung†;P. Redecker;D. Grube;Henryk F. Urbanski§;Bruno Gasnier║;J. Fritschy;M. Gratzl
γ-氨基丁酸（GABA）是大脑中主要的抑制性神经递质。此外，通过垂体GABAA-、GABAB-和GABAC受体发挥作用，它在调节垂体功能方面也起着重要作用。虽然人们普遍认为脑垂体GABA的来源是下丘脑，但我们在此提供的证据表明，GABA的合成也发生在脑垂体本身。采用RT-PCR、原位杂交组织化学、免疫组织化学和免疫电镜技术，对大鼠和恒河猴垂体中GABA合成酶谷氨酸脱羧酶（GAD 67）、囊泡GABA转运体（VIAAT/VGAT）和GABA进行了检测。虽然这些蛋白质被发现在所有的内分泌细胞的中叶，我们发现这些蛋白质的生长激素（GH）生产内分泌细胞的前叶，以及在大鼠GH生产细胞系（GH 3）。此外，GAD酶活性在大鼠垂体和GH 3细胞中很容易检测到。如双重免疫荧光染色所示，发现垂体前叶中的许多内分泌细胞，包括GH细胞以及PRL细胞、TSH细胞、ACTH细胞和LH/FSH细胞含有GABAA和/或GABAB受体。因此，垂体内GABA合成的新位点的鉴定，即中叶的POMC细胞和前叶的GH细胞以及垂体GABA受体的存在，意味着神经递质GABA在垂体内发生意外的自分泌/旁分泌作用。这些结果提示GABA调节垂体功能的一种新的基本机制。
Gamma‐aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the brain. Furthermore, by acting through pituitary GABAA−, GABAB−, and GABAC receptors, it also plays an important role in the regulation of pituitary function. Although it has generally been assumed that the source of this pituitary GABA is the hypothalamus, here we provide evidence that GABA synthesis also occurs within the pituitary gland itself. Using RT‐PCR, in situ hybridization histochemistry, immunohistochemistry, and immunoelectron microscopy, were detected the GABA synthesizing enzyme glutamic acid decarboxylase (GAD 67), the vesicular GABA transporter (VIAAT/VGAT), and GABA in the rat and rhesus monkey pituitary. Although these proteins were found in all of the endocrine cells of the intermediate lobe, we found these proteins in the growth hormone (GH) producing endocrine cells in the anterior lobe only, as well as in a rat GH producing cell line (GH3). In addition, GAD enzyme activity was readily detectable in the rat pituitary and GH3 cells. Many endocrine cells in the anterior pituitary, including GH‐ cells as well as PRL‐, TSH‐, ACTH‐, and LH/FSH‐cells were found to contain GABAA and or GABAB receptors, as shown by double‐immunofluorescence staining. Therefore the identification of a novel site of synthesis of GABA within the pituitary, namely POMC‐cells of the intermediate lobe and GH cells in the anterior lobe and the presence of pituitary GABA receptors, imply unexpected auto/paracrine actions of the neurotransmitter GABA to occur within the pituitary. These results suggest a new basic mechanism in the regulation of pituitary function by GABA.