In vivo and in vitro studies of GABAergic inhibition of prolactin biosynthesis.
In vivo and in vitro studies of GABAergic inhibition of prolactin biosynthesis.
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GABA 能抑制催乳素生物合成的体内和体外研究。
DOI：
10.1159/000124574
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发表时间：
1986
影响因子：
4.1
通讯作者：
V. Höllt
中科院分区：
文献类型：
--
作者：
J. Loeffler;N. Kley;C. Pittius;O. Almeida;V. Höllt
在体外培养的大鼠垂体前叶细胞和体内完整大鼠中研究了γ-氨基丁酸（GABA）对催乳素（PRL）信使核糖核酸（mRNA）水平的抑制作用。通过细胞质RNA与大鼠PRL mRNA互补的放射性标记脱氧核糖核酸探针杂交测定PRL mRNA水平。用GABA（10-100 μ M）孵育垂体前叶培养物，可使PRL mRNA水平呈剂量依赖性降低，半数最大抑制接近1 μ M。该效应呈时间依赖性，停药后可逆。GABA的抑制作用被荷包牡丹碱（10 μ M）拮抗，并被GABAA受体激动剂蝇蕈醇和异谷孢菌素模拟，但不被GABAB激动剂巴氯芬模拟，表明GABAA受体参与PRL mRNA的积累。为了研究内源性GABA对体内PRL生物合成的作用，通过使用GABA转氨酶阻断剂乙烯基GABA和乙醇胺-O-硫酸盐来提高GABA水平。给大鼠注射乙烯基GABA（100或800 mg/kg，每2天1次），可使大鼠腺垂体PRL mRNA水平呈剂量和时间依赖性下降。通过向饮用水中加入乙醇胺-O-硫酸盐（5 mg/ml，250 mg/天）获得了类似的结果。这种治疗导致循环PRL水平迅速下降。这是随后的延迟降低催乳素mRNA的浓度在腺垂体导致短暂的增加激素水平在垂体前叶。结果表明，GABA通过直接作用于垂体催乳细胞上的GABAA受体，对PRL分泌和PRL基因表达具有抑制作用。
The inhibitory action of gamma-aminobutyric acid (GABA) on prolactin (PRL) messenger ribonucleic acid (mRNA) levels was studied in vitro in rat anterior pituitary cells in culture and in intact rats in vivo. PRL mRNA levels were determined by hybridization of cytoplasmic RNA with a radiolabelled deoxyribonucleic acid probe complementary to rat PRL mRNA. Incubation of anterior pituitary cultures with GABA (10-100 microM) produced a dose-dependent decrease in PRL mRNA levels with half-maximal inhibition near 1 microM. The effect was time dependent and reversible after drug withdrawal. Inhibition by GABA was antagonized by bicuculline (10 microM) and mimicked by the GABAA receptor agonists muscimol and isoguvacine, but not with the GABAB agonist baclofen, indicating the involvement of GABAA receptors in the accumulation of PRL mRNA. To investigate the role of endogenous GABA on PRL biosynthesis in vivo, GABA levels were raised by using the GABA transaminase blockers vinyl GABA and ethanolamine-O-sulfate. Injection of vinyl GABA into rats (100 or 800 mg/kg every 2nd day) resulted in a dose- and time-dependent decrease in PRL mRNA levels in rat adenohypophysis. Similar results were obtained by addition of ethanolamine-O-sulfate to the drinking water (5 mg/ml, 250 mg/day). This treatment resulted in a rapid decrease of circulating PRL levels. This was followed by a delayed decrease in PRL mRNA concentrations in the adenohypophysis leading to a transient increase in hormone levels in the anterior pituitary. The results indicate that GABA has an inhibitory role on PRL secretion and PRL gene expression by a direct action at GABAA receptors on pituitary lactotrophs.