Feldman Shaul, Weidenfeld Joseph
Department of Neurology, The Agnes Ginges Center for Neurogenetics, Hadassah University Hospital and Hebrew University-Hadassah Medical School, POB 12000, Jerusalem 91120, Israel.
Brain Res. 2002 Dec 27;958(2):291-6. doi: 10.1016/s0006-8993(02)03581-3.
The site of action of glucocorticoids (GC) in exerting negative feedback upon the hypothalamo-pituitary-adrenocortical (HPA) axis is not yet clear. In the present study we have examined whether dexamethasone (Dex) can inhibit the HPA axis stress responses by acting locally at the hypothalamic level in freely moving male rats. Local micro-injection of Dex in the paraventricular nuclei (PVN; 1 microg) prevented a decrease of CRH-41 content in the median eminence. The PVN Dex injections (0.25-1 microg) also inhibited the rise in plasma ACTH and corticosterone (CS) following short photic stimulation in a dose dependent manner. In PVN Dex-injected rats, i.v. injection of CRH-41 increased serum ACTH and CS levels similar to that observed in rats injected with saline into the PVN indicating normal sensitivity of the pituitary gland to CRH-41. Local injection of [3H]Dex in the PVN showed that only a negligible amount of radioactivity was found in the pituitary. These data indicate that minute amounts of Dex in the PVN, which did not affect the pituitary, blocked the HPA axis responses to photic stimulation. It is suggested that Dex may exert its inhibitory effect on the HPA axis at least in part at the hypothalamic level.
糖皮质激素（GC）对下丘脑 - 垂体 - 肾上腺皮质（HPA）轴施加负反馈的作用位点尚不清楚。在本研究中，我们检测了地塞米松（Dex）是否可通过在自由活动的雄性大鼠下丘脑水平局部起作用来抑制HPA轴应激反应。在室旁核（PVN；1微克）局部微量注射Dex可防止正中隆起中促肾上腺皮质激素释放激素（CRH） - 41含量的降低。PVN注射Dex（0.25 - 1微克）还以剂量依赖方式抑制了短时间光刺激后血浆促肾上腺皮质激素（ACTH）和皮质酮（CS）的升高。在PVN注射Dex的大鼠中，静脉注射CRH - 41可使血清ACTH和CS水平升高，这与向PVN注射生理盐水的大鼠中观察到的情况相似，表明垂体对CRH - 41具有正常敏感性。在PVN局部注射[3H]Dex显示，在垂体中仅发现极少量的放射性。这些数据表明，PVN中微量的Dex（不影响垂体）可阻断HPA轴对光刺激的反应。提示Dex可能至少部分在下丘脑水平对HPA轴发挥其抑制作用。
