Gianotti L, Arvat E, Valetto M R, Ramunni J, Di Vito L, Maccagno B, Camanni F, Ghigo E
Department of Internal Medicine, University of Turin, Italy.
Biol Psychiatry. 1998 Feb 1;43(3):181-7. doi: 10.1016/S0006-3223(97)00014-0.
In anorexia nervosa (AN), growth hormone (GH) hypersecretion and low insulin-like growth factor I (IGF-I) levels are present. It is unclear whether this is due to a peripheral GH resistance and a reduced IGF-I negative feedback on GH secretion or to a primary hypothalamic dysfunction. In AN, in contrast to normal subjects, cholinergic antagonists and agonists, whose action is somatostatin (SS)-mediated, have reduced and absent effects on the GH response to growth hormone-releasing hormone (GHRH). Since arginine, another substance acting via inhibition of SS, maintains its potentiating effect on GH secretion in AN, it has been hypothesized that somewhat specific alteration of the SS-mediated cholinergic influence may be present in this condition. To further clarify the neural control of AH secretion in AN, we evaluated the effects of beta-adrenergic agonists and antagonists, which are known to inhibit and increase, respectively, the GHRH-induced GH secretion in normal subjects.
We studied the effect of atenolol (ATE), a beta 1-adrenergic antagonist, and salbutamol (SALB), a beta 2-adrenergic agonist, on the GHRH-induced GH release in 10 patients with AN and in 10 normal age-matched women (NW).
Basal GH levels were higher, whereas IGF-I were lower in AN than in NW. The GHRH-induced GH rise in AN was higher than that in NW. ATE significantly enhanced the GH response to GHRH in NW, but not in AN. The GH responses to GHRH after ATE pretreatment were similar in NW and in AN. The GH response to GHRH was inhibited by SALB in both NW and AN. The GH responses to GHRH after SALB pretreatment were similar in NW and AN.
These data reveal an exaggerated somatotrope responsiveness to GHRH in AN that is not further increased by beta-adrenergic blockade, while is abolished by beta-adrenergic activation. This suggests that an impairment of beta-adrenergic influence on GH secretion is present in anorexia nervosa.
在神经性厌食症（AN）中，存在生长激素（GH）分泌过多和胰岛素样生长因子I（IGF-I）水平降低的情况。目前尚不清楚这是由于外周GH抵抗以及IGF-I对GH分泌的负反馈减少，还是由于原发性下丘脑功能障碍。与正常受试者相比，在AN中，其作用由生长抑素（SS）介导的胆碱能拮抗剂和激动剂对GH对生长激素释放激素（GHRH）的反应作用减弱或无作用。由于精氨酸是另一种通过抑制SS起作用的物质，在AN中仍保持其对GH分泌的增强作用，因此推测在这种情况下可能存在SS介导的胆碱能影响的某种特定改变。为了进一步阐明AN中GH分泌的神经控制，我们评估了β-肾上腺素能激动剂和拮抗剂的作用，已知它们分别抑制和增加正常受试者中GHRH诱导的GH分泌。
我们研究了β1-肾上腺素能拮抗剂阿替洛尔（ATE）和β2-肾上腺素能激动剂沙丁胺醇（SALB）对10例AN患者和10例年龄匹配的正常女性（NW）中GHRH诱导的GH释放的影响。
AN患者的基础GH水平较高，而IGF-I水平低于NW。AN中GHRH诱导的GH升高高于NW。ATE显著增强了NW中GH对GHRH的反应，但在AN中未增强。ATE预处理后，NW和AN中GH对GHRH的反应相似。SALB在NW和AN中均抑制了GH对GHRH的反应。SALB预处理后，NW和AN中GH对GHRH的反应相似。
这些数据表明，AN中生长激素细胞对GHRH的反应过度，β-肾上腺素能阻断不会使其进一步增加，而β-肾上腺素能激活则可消除这种反应。这表明神经性厌食症中存在β-肾上腺素能对GH分泌影响的损害。
