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在神经性厌食症和非典型饮食失调的急性期及恢复期,哌仑西平对胆碱能毒蕈碱受体的阻断作用与生长激素释放激素诱导的生长激素分泌

Blockade of cholinergic muscarinic receptors by pirenzepine and GHRH-induced GH secretion in the acute and recovery phase of anorexia nervosa and atypical eating disorders.

作者信息

Rolla M, Andreoni A, Belliti D, Cristofani R, Ferdeghini M, Müller E E

机构信息

I Clinica Medica, U.O. di Fisiopatologia dell'Adolescenza, Università di Pisa, Italy.

出版信息

Biol Psychiatry. 1991 Jun 1;29(11):1079-91. doi: 10.1016/0006-3223(91)90250-p.

DOI:10.1016/0006-3223(91)90250-p
PMID:1908328
Abstract

In view of the important role played by the cholinergic system in the neural regulation of growth hormone (GH) secretion, the ability of pirenzepine, a selective antagonist of muscarinic cholinergic receptors, to blunt the GH response to GH-releasing hormone (GHRH) was studied in adolescent females with anorexia nervosa in the acute (AN-AP) five AN-AP patients, administration of GHRH 1-40 (1 microgram/kg IV) evoked a significantly higher GH response than in controls at established intervals, whereas in eight AN-RP and seven AED patients it was higher than in controls at only one (150-min) and two (150-min, 180-min) time intervals, respectively. In the AN-AP patients, pretreatment with pirenzepine (0.6 mg/kg IV) only partially blocked the GH response to GHRH, whereas in the same AN-AP patients tested during recovery, and in AN-RP and AED patients, the drug completely suppressed the GH response to GHRH, as it did in controls. In view of pirenzepine's mechanism of action, these findings are best explained by the existence in the hypothalamus of AN-AP patients of a cholinergic hypertone and/or a diminished somatostatinergic function. Evaluation of the clinical and hormonal characteristics of the anorectic patients studied would indicate that factors other than undernutrition and its biological consequences, which subside in the recovery stage of the disease and are not present in AED patients, contribute to the anomalous GH response pattern of AN-AP patients.

摘要

鉴于胆碱能系统在生长激素(GH)分泌的神经调节中发挥的重要作用,本研究探讨了毒蕈碱胆碱能受体选择性拮抗剂哌仑西平抑制GH对生长激素释放激素(GHRH)反应的能力。在急性神经性厌食症青少年女性(AN-AP)中,5例AN-AP患者静脉注射GHRH 1-40(1微克/千克)后,在既定时间间隔内,其GH反应显著高于对照组;而在8例神经性厌食症康复期患者(AN-RP)和7例青春期情绪障碍患者(AED)中,分别仅在1个(150分钟)和2个(150分钟、180分钟)时间间隔内高于对照组。在AN-AP患者中,预先静脉注射哌仑西平(0.6毫克/千克)仅部分阻断了GH对GHRH的反应;而在恢复期间接受测试的相同AN-AP患者以及AN-RP和AED患者中,该药物完全抑制了GH对GHRH的反应,与对照组情况相同。鉴于哌仑西平的作用机制,这些发现最好的解释是AN-AP患者下丘脑存在胆碱能张力过高和/或生长抑素能功能减弱。对所研究的厌食症患者的临床和激素特征进行评估表明,除了营养不良及其生物学后果(这些在疾病恢复阶段会消退且在AED患者中不存在)之外,还有其他因素导致了AN-AP患者异常的GH反应模式。

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Endocr Rev. 2008 Aug;29(5):535-59. doi: 10.1210/er.2007-0036. Epub 2008 Apr 24.
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GH/IGF-I axis in anorexia nervosa.
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