Zelena Dóra, Domokos Agnes, Barna István, Mergl Zsuzsa, Haller József, Makara Gábor B
Institute of Experimental Medicine, 1083 Budapest, Hungarian Academy of Sciences, Szigony 43, Hungary.
Endocrinology. 2008 May;149(5):2576-83. doi: 10.1210/en.2007-1537. Epub 2008 Feb 14.
In adulthood the hypothalamo-pituitary-adrenal axis is controlled by both CRH and arginine vasopressin (AVP). However, in neonates CRH secretion is very low, whereas AVP secretion is fully functional. This suggests that the role of AVP is more pronounced in young than in adult rats. We investigated the role of AVP by studying stress responses in 5, 10, and 20-d-old AVP-deficient Brattleboro rats. Two different stressors were applied: 24-h maternal separation and Hypnorm Grove Oxford UK injections. In heterozygous controls (that do express AVP), both stressors increased plasma ACTH and corticosterone. The ACTH stress response disappeared in AVP-deficient rats, demonstrating that during the perinatal period, the secretion of this hormone is controlled by AVP. Surprisingly, corticosterone responses remained intact in AVP-deficient rats. Similar findings were obtained after 1-, 4-, 12-, and 24-h long maternal separations. Thus, preserved corticosterone stress responses were not explained by changes in the timing of ACTH secretion. In vitro experiments suggested that the dissociation of ACTH and corticosterone stress responses can only be partly explained by higher ACTH responsiveness of the adrenal cortex in AVP-deficient rats. Together, our results show that in neonatal periods, AVP is crucial for the expression of ACTH stress responses, but neither AVP nor ACTH is necessary for the induction of corticosterone stress responses. Discrepant ACTH and corticosterone stress responses may reflect compensatory mechanisms activated by AVP deficiency, but disparate findings suggest that they rather depict a neonate-specific mechanism of hypothalamo-pituitary-adrenal-axis control.
在成年期，下丘脑 - 垂体 - 肾上腺轴受促肾上腺皮质激素释放激素（CRH）和精氨酸加压素（AVP）共同控制。然而，在新生儿中，CRH分泌非常低，而AVP分泌功能完全正常。这表明AVP在幼鼠中的作用比成年大鼠更为显著。我们通过研究5日龄、10日龄和20日龄的AVP缺陷型布拉特洛维大鼠的应激反应来探究AVP的作用。应用了两种不同的应激源：24小时母婴分离和Hypnorm（英国牛津格罗夫）注射。在杂合子对照组（确实表达AVP）中，两种应激源均增加了血浆促肾上腺皮质激素（ACTH）和皮质酮水平。在AVP缺陷型大鼠中，ACTH应激反应消失，这表明在围产期，这种激素的分泌受AVP控制。令人惊讶的是，AVP缺陷型大鼠的皮质酮应激反应仍然完好。在1小时、4小时、12小时和24小时的母婴分离后也获得了类似的结果。因此，ACTH分泌时间的变化并不能解释皮质酮应激反应的保留。体外实验表明，ACTH和皮质酮应激反应的分离只能部分由AVP缺陷型大鼠肾上腺皮质对ACTH的更高反应性来解释。总之，我们的结果表明，在新生儿期，AVP对ACTH应激反应的表达至关重要，但AVP和ACTH对于皮质酮应激反应的诱导都不是必需的。ACTH和皮质酮应激反应的差异可能反映了由AVP缺乏激活的代偿机制，但不同的结果表明它们更描绘了一种新生儿特异性的下丘脑 - 垂体 - 肾上腺轴控制机制。
