Guillaume-Gentil C, Rohner-Jeanrenaud F, Abramo F, Bestetti G E, Rossi G L, Jeanrenaud B
Laboratoires de Recherches Métaboliques, Faculty of Medicine, University of Geneva, Switzerland.
Endocrinology. 1990 Apr;126(4):1873-9. doi: 10.1210/endo-126-4-1873.
Adrenalectomy has been shown to reverse most facets of the syndrome of the genetically obese fa/fa rat. However, a detailed analysis of the hypothalamo-pituitary-adrenal (HPA) axis in these animals is lacking. In the present study, morning corticosteronemia was higher in obese rats of both sexes than in lean ones, whereas evening corticosteronemia was higher only in obese male rats. The HPA axis was further investigated using stressful stimuli. Immobilization, ether, and cold stresses resulted in greater corticosterone levels in obese than in lean animals. These abnormalities consisted in upward shifts of the corticosterone response in obese females and absolute increases in that of obese males, indicating that such alterations were more pronounced in obese male than obese female rats. Due to this, the putative origin of the increased corticosterone output of obese rats was studied in males. Greater levels of ACTH were reached in obese than in lean rats when submitted to a cold stress (6 C). Dexamethasone produced a complete suppression of corticosterone output in both lean and obese rats. During the recovery from such suppression, corticosterone levels rose to higher values in obese than in lean rats. This observation together with the greater cold-induced ACTH output in obese rats suggest that the increased activity of the HPA axis of these animals is of central origin. Whatever its precise etiology within the central nervous system, it is proposed that the increased HPA axis activity in obese rats and its resultant hypercorticism play a role in the establishment and maintenance of their syndrome.
肾上腺切除术已被证明可逆转遗传性肥胖fa/fa大鼠综合征的大多数方面。然而，目前尚缺乏对这些动物下丘脑-垂体-肾上腺（HPA）轴的详细分析。在本研究中，肥胖大鼠无论雌雄，早晨的皮质酮血症均高于瘦大鼠，而仅肥胖雄性大鼠的夜间皮质酮血症较高。使用应激刺激对HPA轴进行了进一步研究。固定、乙醚和冷应激导致肥胖动物的皮质酮水平高于瘦动物。这些异常表现为肥胖雌性大鼠皮质酮反应的向上偏移以及肥胖雄性大鼠皮质酮反应的绝对增加，表明这种改变在肥胖雄性大鼠中比在肥胖雌性大鼠中更为明显。因此，在雄性大鼠中研究了肥胖大鼠皮质酮输出增加的假定来源。在冷应激（6℃）下，肥胖大鼠的促肾上腺皮质激素（ACTH）水平高于瘦大鼠。地塞米松可完全抑制瘦大鼠和肥胖大鼠的皮质酮输出。在从这种抑制状态恢复期间，肥胖大鼠的皮质酮水平升至比瘦大鼠更高的值。这一观察结果以及肥胖大鼠中冷诱导的ACTH输出增加表明，这些动物HPA轴活性的增加源于中枢。无论其在中枢神经系统内的确切病因是什么，有人提出肥胖大鼠HPA轴活性增加及其导致的高皮质醇血症在其综合征的发生和维持中起作用。
