Cunningham J J, Meara P A, Lee R Y, Bode H H
Children's Service, Shriners Burns Institute, Boston, Massachusetts.
Am J Physiol. 1988 Aug;255(2 Pt 1):E213-7. doi: 10.1152/ajpendo.1988.255.2.E213.
Bolus intracerebroventricular delivery of corticotropin-releasing factor (CRF) elicits acute responses of both the pituitary-adrenal axis and the sympathetic nervous system. We examined whether these stresslike responses could be maintained over a period of days by central delivery of CRF in nonstressed rats, as would be predicted if this peptide participates in the central nervous system regulation of chronic stress. CRF (4.3 or 21.5 micrograms/day) was continuously delivered into the cerebral ventricle via Alzet minipumps. In contrast to saline-infused controls, rats receiving CRF exhibited elevated excretions of corticosterone, norepinephrine, and urea nitrogen for several days. Thereafter, an attenuation of CRF responsiveness occurred when corticosterone excretion returned to basal levels despite continued central CRF infusion. However, CRF delivered intravenously during attenuation stimulated adrenocorticotropic hormone and corticosterone secretion, implicating a hypothalamic rather than pituitary locus for central CRF resistance. The present data do not permit a conclusion on whether the attenuation of the CRF response with time is the result of an ultrashort-loop negative-feedback mechanism or CRF receptor desensitization.
脑室内注射促肾上腺皮质激素释放因子（CRF）能引发垂体-肾上腺轴和交感神经系统的急性反应。我们研究了在无应激的大鼠中，通过中枢给予CRF，这些类似应激的反应是否能在数天内持续存在，就像如果这种肽参与慢性应激的中枢神经系统调节所预测的那样。通过Alzet微型泵将CRF（4.3或21.5微克/天）持续注入脑室。与注入生理盐水的对照组相比，接受CRF的大鼠在数天内皮质酮、去甲肾上腺素和尿素氮的排泄量升高。此后，尽管继续进行中枢CRF输注，但当皮质酮排泄量恢复到基础水平时，CRF反应性出现衰减。然而，在反应衰减期间静脉注射CRF刺激了促肾上腺皮质激素和皮质酮的分泌，这表明中枢CRF抵抗的部位在下丘脑而非垂体。目前的数据无法得出关于CRF反应随时间衰减是超短环负反馈机制还是CRF受体脱敏的结果的结论。
