Matta S G, Fu Y, Valentine J D, Sharp B M
Endocrine Neuroscience Laboratory, Minneapolis Medical Research Foundation, MN 55404, USA.
Psychoneuroendocrinology. 1998 Feb;23(2):103-13. doi: 10.1016/s0306-4530(97)00079-6.
Nicotine has been shown to be a potent stimulus for the secretion of the stress-responsive hormones, adrenocorticotropin (ACTH) and prolactin. This paper reviews the findings by our laboratory and others that demonstrate the polysynaptic pathways involved in the neuroendocrine responses to systemic nicotine. It will focus primarily on the hypothalamo-pituitary-adrenal (HPA) axis and the effect of nicotine on ACTH secretion, with supplementary information on prolactin secretion, where relevant. Data are presented demonstrating that nicotine acts via a central mechanism to stimulate indirectly the release of ACTH from the anterior pituitary corticotropes. Nicotine does not appear to act directly at the hypothalamic paraventricular nucleus (PVN), the site of the corticotropin-releasing hormone (CRH) neurons crucial to the regulation of ACTH. However, brainstem catecholaminergic regions projecting to the PVN showed a regionally selective and dose-dependent sensitivity to nicotine, particularly the noradrenergic/adrenergic nucleus tractus solitarius (NTS). A reduction in the modulatory effect of these catecholamines (by neurotoxic lesion, synthetic enzyme inhibitors or adrenergic receptor antagonists) resulted in an inhibition of nicotine-stimulated ACTH secretion. In addition, blockade of nicotinic cholinergic receptors (NAchRs) in the brainstem by the antagonist, mecamylamine, resulted in a dose-dependent reduction in norepinephrine (NE) release from terminals in the PVN, and a concomitant reduction in plasma ACTH. The differential sensitivity of these receptors to the nicotinic agonists, cytisine and nicotine, reflects the heterogeneity of the NAchR subtypes involved. The desensitization characteristics of the neuroendocrine responses to both acute and chronic nicotine exposure are indicative of an alteration in these NAchRs.
尼古丁已被证明是应激反应激素促肾上腺皮质激素（ACTH）和催乳素分泌的有效刺激物。本文综述了我们实验室及其他研究机构的发现，这些发现证明了参与对全身尼古丁神经内分泌反应的多突触通路。本文将主要聚焦于下丘脑 - 垂体 - 肾上腺（HPA）轴以及尼古丁对ACTH分泌的影响，并在相关情况下提供关于催乳素分泌的补充信息。所呈现的数据表明，尼古丁通过一种中枢机制间接刺激垂体前叶促肾上腺皮质细胞释放ACTH。尼古丁似乎并不直接作用于下丘脑室旁核（PVN），而PVN是对ACTH调节至关重要的促肾上腺皮质激素释放激素（CRH）神经元所在的部位。然而，投射到PVN的脑干儿茶酚胺能区域对尼古丁表现出区域选择性和剂量依赖性敏感性，尤其是去甲肾上腺素能/肾上腺素能孤束核（NTS）。这些儿茶酚胺的调节作用降低（通过神经毒性损伤、合成酶抑制剂或肾上腺素能受体拮抗剂）会导致尼古丁刺激的ACTH分泌受到抑制。此外，拮抗剂美加明对脑干烟碱型胆碱能受体（NAchRs）的阻断导致PVN终末去甲肾上腺素（NE）释放呈剂量依赖性减少，同时血浆ACTH也相应减少。这些受体对烟碱激动剂金雀花碱和尼古丁的不同敏感性反映了所涉及的NAchR亚型的异质性。对急性和慢性尼古丁暴露的神经内分泌反应的脱敏特征表明这些NAchRs发生了改变。
