Müller E E, Rolla M
Department of Pharmacology, Chemotherapy and Toxicology, University of Milan, Italy.
Psychiatry Res. 1996 Apr 16;62(1):51-63. doi: 10.1016/0165-1781(96)02989-7.
A series of studies was devised in both an experimental model of food deprivation, i.e., beagle dogs undergoing a progressive reduction of calorie intake and adolescent females with anorexia nervosa (AN) in the acute and recovery phase, and in patients with atypical eating disorders. The studies were aimed at ascertaining whether the alleged function of the hypothalamic system inhibitory to growth hormone (GH) secretion, i.e., the somatostatinergic, may account for at least some of the abnormalities of GH secretion present in AN patients (e.g., elevated basal GH levels, paradoxical GH rise after glucose or thyrotropin releasing hormone, etc). Caloric restricted dogs or patients with eating disorders were given an intravenous injection of the physiologic GH-releasing peptide GHRH alone or preceded by pirenzepine, a muscarinic cholinergic antagonist reportedly capable of eliciting hypothalamic release of somatostatin (SS), or pyridostigmine, a muscarinic cholinergic agonist which, conversely, would restrain hypothalamic release of SS. In addition, dogs were challenged with acute administration of glucose or thyrotropin-releasing hormone, compounds also thought to act via somatostatinergic influences. Data obtained in dogs under caloric restriction or in AN patients in the acute phase of the disease with drugs affecting cholinergic transmission suggest that the latter is increased in both conditions (only partial suppression of the GHRH-induced GH rise with pirenzepine, failure of pyridostigmine to further enhance the GH response to GHRH). Instead, in the same AN patients in the acute phase tested during recovery, in AN patients during the recovery phase, and in patients with atypical eating disorders, pirenzepine completely suppressed the GH response to GHRH, as it did in controls. Finally, data obtained on basal and GHRH-stimulated GH release in dogs given glucose or thyrotropin-releasing hormone and in AN patients given arginine, another compound thought to act via inhibition of somatostatinergic influences, do not support the view that somatostatinergic function is impaired in states of food deprivation.
一系列研究在两种情况下展开，一种是食物剥夺的实验模型，即比格犬经历卡路里摄入量的逐渐减少，以及处于急性和康复期的神经性厌食症（AN）青少年女性，另一种是患有非典型饮食失调的患者。这些研究旨在确定下丘脑系统抑制生长激素（GH）分泌的所谓功能，即生长抑素能系统，是否可以解释AN患者中存在的至少一些GH分泌异常（例如，基础GH水平升高、葡萄糖或促甲状腺激素释放激素后GH反常升高，等等）。对热量受限的犬或饮食失调患者单独静脉注射生理性GH释放肽GHRH，或在注射前先注射哌仑西平（一种据报道能够引发下丘脑释放生长抑素（SS）的毒蕈碱胆碱能拮抗剂）或吡啶斯的明（一种毒蕈碱胆碱能激动剂，相反，它会抑制下丘脑释放SS）。此外，对犬进行急性葡萄糖或促甲状腺激素释放激素给药挑战，这些化合物也被认为是通过生长抑素能影响起作用的。在热量受限的犬或疾病急性期的AN患者中使用影响胆碱能传递的药物所获得的数据表明，在这两种情况下胆碱能传递均增强（哌仑西平仅部分抑制GHRH诱导的GH升高，吡啶斯的明未能进一步增强GH对GHRH的反应）。相反，在康复期测试的同一急性期AN患者、康复期的AN患者以及非典型饮食失调患者中，哌仑西平完全抑制了GH对GHRH的反应，就像在对照组中一样。最后，在给予葡萄糖或促甲状腺激素释放激素的犬以及给予精氨酸（另一种被认为通过抑制生长抑素能影响起作用的化合物）的AN患者中获得的关于基础和GHRH刺激的GH释放的数据，并不支持食物剥夺状态下生长抑素能功能受损的观点。
