Volpi R, Caffarra P, Scaglioni A, Maestri D, Chiodera P, Coiro V
Chair of Medical Clinic, University of Parma, Italy.
J Neural Transm Park Dis Dement Sect. 1994;7(1):1-11. doi: 10.1007/BF02252658.
Naloxone is unable to stimulate ACTH/cortisol secretion in patients with de novo Parkinson's disease, suggesting a reduced endogenous opioid control of the hypothalamic-pituitary-adrenal axis in parkinsonian patients. In the present study we examined whether Parkinson's disease also impairs the secretion of LH, which is under the inhibitory control of different opioid peptides than ACTH/cortisol. In addition, we examined whether a chronic dopaminergic therapy for at least one year with levodopa (450 mg/day) plus benserazide (112.5 mg/day) in 3 divided oral doses/day of Madopar modifies the ACTH/cortisol and/or the LH response to naloxone (4 mg as an i.v. bolus plus 10 mg infused in 2 hours). Ten parkinsonian patients (aged 52-62 years) and 8 normal controls (50-60 years) were tested with naloxone and in a different occasion with normal saline. The parkinsonian patients were tested both before and after dopaminergic treatment. Tests started at 09.00 h and lasted 2.5 hours. Basal ACTH/cortisol and LH levels were similar in all groups. During saline tests, ACTH/cortisol levels showed a slight physiological decline in all groups, whereas LH levels remained constant. Naloxone administration significantly increased the plasma levels of ACTH/cortisol and LH in the normal controls, but not in the parkinsonian patients before the dopaminergic treatment. In contrast, dopaminergic therapy restored significant ACTH/cortisol and LH responses to naloxone in parkinsonian patients. In fact, after levodopa plus benserazide, naloxone-induced ACTH, cortisol and LH increments in parkinsonian patients were significantly higher than before therapy and were indistinguishable from those observed in the normal controls. These data suggest that in men Parkinson's-related dopaminergic alterations may underlie the defective endogenous opioid control of ACTH/cortisol and LH secretion.
纳洛酮无法刺激初发帕金森病患者的促肾上腺皮质激素/皮质醇分泌，这表明帕金森病患者下丘脑-垂体-肾上腺轴的内源性阿片类物质调控功能减弱。在本研究中，我们探究了帕金森病是否也会损害促黄体生成素（LH）的分泌，LH受与促肾上腺皮质激素/皮质醇不同的阿片肽抑制性调控。此外，我们还研究了3名帕金森病患者（年龄52 - 62岁）接受左旋多巴（450毫克/天）加苄丝肼（112.5毫克/天），每日分3次口服，至少持续一年的慢性多巴胺能治疗，即服用美多芭后，是否会改变促肾上腺皮质激素/皮质醇和/或LH对纳洛酮（静脉推注4毫克加2小时内输注10毫克）的反应。10名帕金森病患者和8名正常对照者（年龄50 - 60岁）接受了纳洛酮测试，并在不同时间接受了生理盐水测试。帕金森病患者在多巴胺能治疗前后均进行了测试。测试于09:00开始，持续2.5小时。所有组的基础促肾上腺皮质激素/皮质醇和LH水平相似。在生理盐水测试期间，所有组的促肾上腺皮质激素/皮质醇水平均出现轻微生理性下降，而LH水平保持不变。纳洛酮给药显著提高了正常对照者的血浆促肾上腺皮质激素/皮质醇和LH水平，但在多巴胺能治疗前的帕金森病患者中未出现此现象。相反，多巴胺能治疗恢复了帕金森病患者对纳洛酮的显著促肾上腺皮质激素/皮质醇和LH反应。实际上，服用左旋多巴加苄丝肼后，帕金森病患者中纳洛酮诱导的促肾上腺皮质激素、皮质醇和LH增量显著高于治疗前，且与正常对照者中观察到的增量无差异。这些数据表明，在男性中，帕金森病相关的多巴胺能改变可能是促肾上腺皮质激素/皮质醇和LH分泌的内源性阿片类物质调控缺陷的基础。
