NEONATAL HANDLING ALTERS ADRENOCORTICAL NEGATIVE FEEDBACK SENSITIVITY AND HIPPOCAMPAL TYPE-II GLUCOCORTICOID RECEPTOR-BINDING IN THE RAT
NEONATAL HANDLING ALTERS ADRENOCORTICAL NEGATIVE FEEDBACK SENSITIVITY AND HIPPOCAMPAL TYPE-II GLUCOCORTICOID RECEPTOR-BINDING IN THE RAT
复制标题
DOI：
10.1159/000125287
复制
发表时间：
1989-11-01
影响因子：
4.1
通讯作者：
SARRIEAU, A
中科院分区：
文献类型：
--
作者：
MEANEY, MJ;AITKEN, DH;SARRIEAU, A
在生命的前3周，每天处理(H)的成年大鼠的肾上腺皮质对压力的反应发生了显着的变化。我们发现，在应激终止期间和之后，H组动物分泌的ACTH和皮质酮(B)比未处理(NH)对照组的少。相反，在每日周期的任何时间点，H和NH动物的基础B分泌量没有差异，肾上腺皮质对外源性OCRF或ACTH的反应也没有差异。此外，H和NH动物对B的清除率相似。H组动物对B或地塞米松对应激诱导的肾上腺皮质活动的抑制作用比NH组动物更敏感。在一项剂量-反应研究中，两种糖皮质激素在测试前3小时在H动物中更大程度地抑制了肾上腺皮质对20分钟束缚应激的反应。处理增加了成年动物海马区II型糖皮质激素受体结合容量(.apprx.容量增加50%，亲和力没有变化)。下丘脑或垂体中的II型受体结合能力和海马区的I型受体结合能力都没有因搬运而发生变化。长期给予B(5 mg/kg/d)处理后，与生理盐水处理的H动物相比，B处理的H动物的海马II型受体结合能力显著降低，并且与生理盐水处理的NH动物没有区别。与生理盐水处理的H动物相比，H动物，如NH动物，在应激结束后分泌高B。这些数据表明，海马II型糖皮质激素受体的增加是肾上腺皮质应激反应处理效应的关键特征。受体的增加似乎使H动物对循环中高水平糖皮质激素的负反馈效应更加敏感，对随后的肾上腺皮质活动施加了更大的抑制控制。
Adult rats handled (H) daily for the first 3 weeks of life show a dramatically altered adrenocortical response to stress. We found that H animals secreted less ACTH and corticosterone (B) during and following the termination of stress than did nonhandled (NH) controls. In contrast, H and NH animals did not differ in basal B secretion at any point in the diurnal cycle, nor in adrenocortical responses to exogenously administered oCRF or ACTH. Moreover, the clearance rate for B was similar in H and NH animals. H animals were more sensitive than NH animals to the inhibitory effects of either B or dexamethasone on stress-induced adrenocortical activity. In a dose-response sutdy, both glucocorticoids administered 3 h prior to testing suppressed the adrenocortical response to a 20-min restraint stress to a greater extent in the H animals. Handling increased type II, glucocorticoid receptor binding capacity in the hippocampus of adult animals (.apprx. 50% increase in capacity, with no change in affinity). There were no handling-induced changes in type II receptor binding capacity in the hypothalamus or pituitary, nor in type I receptor binding capacity in the hippocampus. Following chronic (5 mg/kg/day) treatment with B, hippocampal type II receptor binding capacity was significantly reduced in the B-treated H animals, compared with saline-treated H animals, and indistinguishable from saline-treated NH animals. Down-regulated H animals, like NH animals, hypersecreted B following the termination of stress in comparison to the saline-treated H animals. These data suggest that the increase in hippocampal type II glucocorticoid receptors is a critical feature for the handling effect on the adrenocortical stress response. The increase in receptors appears to render the H animals more sensitive to the negative feedback effects of the high levels of circulating glucocorticoids, exerting a greater inhibitory control over subsequent adrenocortical activity.