van Oers H J, de Kloet E R, Li C, Levine S
Department of Psychology, University of Delaware, Newark 19716-2577, USA.
Endocrinology. 1998 Jun;139(6):2838-46. doi: 10.1210/endo.139.6.6037.
Glucocorticoid feedback can be viewed as having two modes of operation: proactive and reactive. "Proactive" feedback maintains basal activity of the hypothalamic-pituitary-adrenal axis, whereas the termination of stress-induced hypothalamic-pituitary-adrenal activity is facilitated by "reactive" feedback. In the present study we studied the ontogeny of both feedback modes and tested the hypothesis that the development of feedback depends on mother-pup interaction. On postnatal day 9 or 12, pups were deprived (DEP) of the dam for 24 h; nondeprived pups of the same age served as controls. The pups were adrenalectomized (ADX) at the end of deprivation and given corticosterone (CORT) replacement by either injection or pellet implants using the following two designs: first at the time of adrenalectomy (ADX) to test the role of CORT in the maintenance of basal ACTH levels, and then 3 h after ADX, to investigate CORT suppression of elevated ACTH levels induced by prior ADX. Regarding proactive feedback, the results showed that injection of CORT at the time of ADX was only partially effective in preventing ACTH elevations, whereas CORT pellets maintained basal levels of ACTH in all ADX pups. The reactive mode of negative feedback in nondeprived pups was resistant to CORT injection, whereas the CORT pellet resulted in a return to basal levels within 60 min. Maternal deprivation did not affect proactive feedback, but caused a more sustained increase in ACTH levels and a failure to return to basal levels 3 h after ADX despite significantly higher levels of circulating CORT in these DEP pups. It is concluded that 1) proactive and reactive modes of negative feedback are operative, provided the pups are maintained on chronic replacement with CORT; 2) DEP impairs the reactive, rather than the proactive, mode of feedback inhibition in the neonate.
主动型和反应型。“主动”反馈维持下丘脑 - 垂体 - 肾上腺轴的基础活性，而“反应”反馈则促进应激诱导的下丘脑 - 垂体 - 肾上腺活性的终止。在本研究中，我们研究了这两种反馈模式的个体发生，并检验了反馈发育取决于母幼互动的假说。在出生后第9天或第12天，幼崽被剥夺与母鼠接触24小时；相同年龄未被剥夺的幼崽作为对照。在剥夺结束时对幼崽进行肾上腺切除术（ADX），并使用以下两种设计通过注射或植入丸剂给予皮质酮（CORT）替代：首先在肾上腺切除时（ADX）以测试CORT在维持基础促肾上腺皮质激素（ACTH）水平中的作用，然后在ADX后3小时，以研究CORT对先前ADX诱导的升高的ACTH水平的抑制作用。关于主动反馈，结果表明在ADX时注射CORT在预防ACTH升高方面仅部分有效，而CORT丸剂在所有ADX幼崽中维持ACTH的基础水平。未被剥夺的幼崽中负反馈的反应模式对CORT注射有抗性，而CORT丸剂导致在60分钟内恢复到基础水平。母体剥夺不影响主动反馈，但导致ACTH水平更持续的升高，并且尽管这些被剥夺幼崽中循环CORT水平显著更高，但在ADX后3小时未能恢复到基础水平。得出的结论是：1）只要幼崽持续接受CORT替代，负反馈的主动和反应模式都是有效的；2）剥夺损害了新生儿反馈抑制的反应模式，而非主动模式。
