Panzeri G, Torsello A, Cella S G, Müller E E, Locatelli V
Department of Pharmacology, School of Medicine, University of Milan, Italy.
Proc Soc Exp Biol Med. 1990 Apr;193(4):301-5. doi: 10.3181/00379727-193-43039.
The involvement of the cholinergic system in growth hormone (GH) secretion has acquired increased importance in the last few years. In rats, pretreatment with muscarinic cholinergic agonists potentiates the GH release induced by GH-releasing hormone (GHRH), via inhibition of somatostatin (SRIF) release from the hypothalamus. The aim of this study was to validate the use of cholinergic agonists to probe the functional activity of the hypothalamic SRIF system. It is known that hypothalamic SRIF displays an age-related increase in its functional activity; therefore, rats from 10 days to 29 months of age were used and challenged with GHRH following acute administration of pilocarpine, a cholinergic muscarinic agonist. Following administration of GHRH alone there was an age-related decline in GH responsiveness. Administration of pilocarpine potentiated the GH response to GHRH during the entire life-span of the rats, the only exception being 10-day-old rats in which the drug was without effect. Pilocarpine, though effective in potentiating the GH response to GHRH, did not restore, in senescent rats, GH stimulation to the level of that present in young (3-month old) or adult rats (8-month old). However, the drug was effective in rejuvenating the GH response to GHRH of the older rats (29- and 18-month old) to the level of 15-month-old rats. The present results indicate that modulation of the GH response to GHRH by pilocarpine is consonant with the known changes in the activity of hypothalamic SRIF. Cholinergic drugs may therefore represent a valuable tool to assess SRIF function in physiologic or pathologic conditions of GH secretion, and, in addition, to potentiate GH release during a course of GHRH therapy.
胆碱能系统参与生长激素（GH）分泌这一现象在过去几年中愈发受到重视。在大鼠中，用毒蕈碱型胆碱能激动剂预处理可增强生长激素释放激素（GHRH）诱导的GH释放，其机制是通过抑制下丘脑生长抑素（SRIF）的释放。本研究的目的是验证使用胆碱能激动剂来探究下丘脑SRIF系统的功能活性。已知下丘脑SRIF的功能活性会随年龄增长而增强；因此，本研究使用了10日龄至29月龄的大鼠，并在急性给予毒蕈碱型胆碱能激动剂毛果芸香碱后，用GHRH对其进行刺激。单独给予GHRH后，GH反应性呈现出与年龄相关的下降。在大鼠的整个生命周期中，给予毛果芸香碱均可增强GH对GHRH的反应，唯一的例外是10日龄大鼠，该药物对其无效。毛果芸香碱虽然能有效增强GH对GHRH的反应，但在衰老大鼠中，它并未将GH刺激恢复到年轻（3月龄）或成年大鼠（8月龄）的水平。然而，该药物能有效使老年大鼠（29月龄和18月龄）对GHRH的GH反应恢复到15月龄大鼠的水平。目前的结果表明，毛果芸香碱对GH对GHRH反应的调节与下丘脑SRIF活性的已知变化一致。因此，胆碱能药物可能是评估GH分泌生理或病理状态下SRIF功能的有价值工具，此外，还可在GHRH治疗过程中增强GH释放。
