Kiem D T, Barna I, Koenig J I, Makara G B
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.
Neuroendocrinology. 1995 Feb;61(2):152-8. doi: 10.1159/000126835.
We studied the effect of glucocorticoid pretreatment, mediobasal hypothalamus lesion (MBHL) and the interaction between clonidine and yohimbine in male Wistar rats to elucidate the sites and/or mechanisms of endocrine actions of alpha 2-antagonists. The pretreatment of 1 mg/kg s.c. dexamethasone for 4 days effectively prevented the stimulatory effect of alpha 2-antagonists yohimbine (5 mg/kg i.p.) and CH-38083 (1 mg/kg i.p.) on adrenocorticotropin (ACTH) secretion, while the action of these antagonists on prolactin (PRL) and beta-endorphin (beta E) remained unchanged. The central (i.c.v.) pretreatment of 5 micrograms/rat clonidine failed to antagonize the prolactin (PRL) and beta E releasing effect of yohimbine. However, it inhibited the yohimbine-induced ACTH secretion. MBHL resulted in a significant enhancement in basal plasma PRL and beta-endorphin (beta E) levels. But basal plasma ACTH levels have not been changed. Yohimbine failed to stimulate ACTH secretion in MBH-lesions rats, while PRL and beta E response to the yohimbine was maintained in these animals. This study confirms that the alpha 2-antagonists stimulate ACTH secretion by a corticosteroid-sensitive mechanism which is located centrally. In contrast, alpha 2-antagonists affect PRL and beta E secretion via a corticosteroid-insensitive mechanism located at the periphery, possible within the pituitary gland.
我们研究了糖皮质激素预处理、下丘脑中间基底部损伤（MBHL）以及可乐定与育亨宾之间的相互作用对雄性Wistar大鼠的影响，以阐明α2拮抗剂内分泌作用的部位和/或机制。皮下注射1mg/kg地塞米松预处理4天可有效预防α2拮抗剂育亨宾（腹腔注射5mg/kg）和CH-38083（腹腔注射1mg/kg）对促肾上腺皮质激素（ACTH）分泌的刺激作用，而这些拮抗剂对催乳素（PRL）和β-内啡肽（βE）的作用保持不变。每只大鼠脑室内（i.c.v.）预处理5μg可乐定未能拮抗育亨宾释放催乳素（PRL）和βE的作用。然而，它抑制了育亨宾诱导的ACTH分泌。MBHL导致基础血浆PRL和β-内啡肽（βE）水平显著升高。但基础血浆ACTH水平未发生变化。育亨宾未能刺激MBH损伤大鼠的ACTH分泌，而这些动物对育亨宾的PRL和βE反应得以维持。本研究证实，α2拮抗剂通过位于中枢的皮质类固醇敏感机制刺激ACTH分泌。相比之下，α2拮抗剂通过位于外周（可能在垂体腺内）的皮质类固醇不敏感机制影响PRL和βE的分泌。
