García-García L, Fuentes J A, Manzanares J
Departamento de Farmacologia, Facultad de Farmacia and Instituto Pluridisciplinar, Universidad Complutense de Madrid, Spain.
Brain Res. 1997 Oct 24;772(1-2):115-20. doi: 10.1016/s0006-8993(97)00863-9.
The purpose of the present study was to examine the role of 5-hydroxytryptamine (5-HT) neurons in mediating the effects of stress on proopiomelanocortin (POMC) gene expression in the anterior and intermediate lobes of the pituitary gland. To this aim, the effects of 5-HT depletion induced by administration of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT; 200 microg/rat; i.c.v.; 7 days) were investigated on POMC mRNA levels in the anterior and intermediate lobe of control and restraint-stressed rats. Three hours after brief exposure to diethyl ether (2 min) followed by 60 min of restraint stress increased POMC mRNA levels in the anterior and intermediate lobe of the pituitary. 5,7-DHT neurotoxic lesion, which resulted in a marked depletion of 5-HT (below the level of sensitivity of the neurochemical assay, 6 pg/sample) but not of dopamine or norepinephrine concentrations in the periventricular nucleus of the hypothalamus, had no effect on basal POMC mRNA levels in the anterior or intermediate lobe of the pituitary. However, 5-HT depletion further increased POMC mRNA levels in the anterior pituitary and completely blocked POMC mRNA level enhancement induced in the intermediate lobe of stressed rats. These results suggest a possible inhibitory 5-HT tone on POMC gene expression in the anterior pituitary and a stimulatory 5-HT tone in the intermediate lobe of the pituitary under these experimental conditions of stress. It appears, therefore, that 5-HT exerts a differential regulation of stress-induced activation of POMC gene expression in the anterior and intermediate lobes of the pituitary in male rats.
本研究的目的是检测5-羟色胺（5-HT）神经元在介导应激对垂体前叶和中叶促肾上腺皮质激素原（POMC）基因表达影响中的作用。为此，研究了通过注射神经毒素5,7-二羟色胺（5,7-DHT；200μg/大鼠；脑室内注射；7天）诱导的5-HT耗竭对对照和束缚应激大鼠垂体前叶和中叶POMC mRNA水平的影响。短暂暴露于乙醚（2分钟）后60分钟的束缚应激使垂体前叶和中叶的POMC mRNA水平升高。5,7-DHT神经毒性损伤导致5-HT显著耗竭（低于神经化学检测的灵敏度水平，6pg/样本），但下丘脑室旁核中的多巴胺或去甲肾上腺素浓度未受影响，对垂体前叶或中叶的基础POMC mRNA水平没有影响。然而，5-HT耗竭进一步增加了垂体前叶的POMC mRNA水平，并完全阻断了应激大鼠中叶诱导的POMC mRNA水平升高。这些结果表明，在这些应激实验条件下，5-HT对垂体前叶POMC基因表达可能具有抑制作用，而对垂体中叶具有刺激作用。因此，在雄性大鼠中，5-HT对垂体前叶和中叶应激诱导的POMC基因表达激活发挥了差异性调节作用。
