Magnan E, Cataldi M, Guillaume V, Mazzocchi L, Dutour A, Conte-Devolx B, Giraud P, Oliver C
Laboratoire de Neuroendocrinologie Expérimentale, INSERUM 297, Faculté Médecine Secteur Nord, Marseille, France.
Endocrinology. 1993 Mar;132(3):1247-51. doi: 10.1210/endo.132.3.8095014.
GH secretion is stimulated by the administration of cholinesterase inhibitors (such as pyridostigmine and neostigmine) in several species, including man. On the basis of indirect experiments, it has been postulated that this action is mediated by a decrease in hypothalamic somatostatin release. We have investigated the effect of neostigmine in sheep, since it is possible to collect hypophysial portal blood for GH-releasing hormone (GHRH) and somatostatin determination in this species under a conscious unstressed state. First, after i.v. injection of neostigmine (1 mg), a significant increase in plasma GH levels and an unequivocal potentiation of the GH response to GHRH were observed. Then, we observed that i.v. injection of neostigmine (1 mg) induced an immediate, short-lasting (30 min), and marked increase in GHRH (126.1 +/- 17 vs. 14.5 +/- 2.1 pg/ml; P < 0.01) levels in hypophysial portal blood of rams chronically implanted with perihypophysial cannulae. No change in somatostatin secretion was recorded during the same period. These data suggest that the stimulating effect of cholinergic drugs on GH secretion is mediated by stimulation of GHRH release. A direct effect of neostigmine at the level of pituitary gland is possible and may explain the potentiation of GHRH-induced GH release.
在包括人类在内的多个物种中，给予胆碱酯酶抑制剂（如吡啶斯的明和新斯的明）可刺激生长激素（GH）分泌。基于间接实验，有人推测这种作用是通过下丘脑生长抑素释放减少介导的。我们研究了新斯的明对绵羊的影响，因为在这种有意识且无应激状态的物种中，可以采集垂体门脉血来测定生长激素释放激素（GHRH）和生长抑素。首先，静脉注射新斯的明（1毫克）后，观察到血浆GH水平显著升高，并且对GHRH的GH反应明确增强。然后，我们观察到，对长期植入垂体周围套管的公羊静脉注射新斯的明（1毫克），可使垂体门脉血中GHRH水平立即出现短暂（30分钟）且显著的升高（126.1±17对14.5±2.1皮克/毫升；P<0.01）。在同一时期未记录到生长抑素分泌的变化。这些数据表明，胆碱能药物对GH分泌的刺激作用是通过刺激GHRH释放介导的。新斯的明在垂体水平可能有直接作用，这可能解释了GHRH诱导的GH释放增强的现象。
