Smallridge R C, Carr F E, Fein H G
Department of Clinical Physiology, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100.
Toxicol Appl Pharmacol. 1991 Apr;108(2):284-95. doi: 10.1016/0041-008x(91)90118-x.
Cholinergic mechanisms have been implicated in the regulation of anterior pituitary hormone secretion. The present study was designed to determine the effect of a single injection of an organophosphate acetylcholinesterase inhibitor, diisopropylfluorophosphate (DFP), on anterior pituitary function in male rats. DFP increased serum ACTH (2.7-fold) and corticosterone (9.1-fold), while suppressing TSH, PRL, LH, and GH by up to 95%. The earliest response was at 1 hr, with a duration of at least 18 hr for TSH and LH. Responses were similar in adrenalectomized animals. After DFP, responses to hypothalamic releasing factors were normal for TSH, GH, and ACTH, but significantly blunted for PRL and LH. TSH suppression was partially prevented by combined therapy with a nicotinic (mecamylamine) and a muscarinic (atropine) antagonist. TSH suppression was partially reversed by immunoneutralization with somatostatin antibody, and PRL suppression was completely prevented by a dopamine antagonist (haloperidol). Atropine alone prevented the effects on corticosterone. TSH pituitary content and TSH-beta mRNA were reduced by 37 and 22%, respectively, by DFP. In contrast, PRL mRNA was unchanged but PRL content was increased 3-fold. We conclude that cholinesterase inhibition evokes a multiplicity of effects on anterior pituitary function. There is a hierarchy of responses, with corticosterone being the most and TSH the least sensitive. There is evidence for inhibition at both the hypothalamic and pituitary levels, involving both nicotinic and muscarinic receptors. Although cholinesterase inhibition is the proximate event, other neurotransmitter pathways involved in TSH and PRL suppression are somatostatin and dopamine, respectively.
胆碱能机制与垂体前叶激素分泌的调节有关。本研究旨在确定单次注射有机磷酸酯类乙酰胆碱酯酶抑制剂二异丙基氟磷酸酯（DFP）对雄性大鼠垂体前叶功能的影响。DFP使血清促肾上腺皮质激素（ACTH）增加2.7倍，皮质酮增加9.1倍，同时使促甲状腺激素（TSH）、催乳素（PRL）、促黄体生成素（LH）和生长激素（GH）最多抑制95%。最早的反应出现在1小时，TSH和LH的持续时间至少为18小时。肾上腺切除的动物反应相似。注射DFP后，TSH、GH和ACTH对下丘脑释放因子的反应正常，但PRL和LH的反应明显减弱。联合使用烟碱样（美加明）和毒蕈碱样（阿托品）拮抗剂可部分预防TSH的抑制。用生长抑素抗体进行免疫中和可部分逆转TSH的抑制，多巴胺拮抗剂（氟哌啶醇）可完全预防PRL的抑制。单独使用阿托品可预防对皮质酮的影响。DFP使垂体TSH含量和TSH-β mRNA分别降低37%和22%。相比之下，PRL mRNA未改变，但PRL含量增加了3倍。我们得出结论，胆碱酯酶抑制对垂体前叶功能产生多种影响。存在反应层次，皮质酮最敏感，TSH最不敏感。有证据表明下丘脑和垂体水平均存在抑制，涉及烟碱样和毒蕈碱样受体。虽然胆碱酯酶抑制是直接事件，但参与TSH和PRL抑制的其他神经递质途径分别是生长抑素和多巴胺。
