O'Donnell D, Larocque S, Seckl J R, Meaney M J
Douglas Hospital Research Center, Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, Canada.
Brain Res Mol Brain Res. 1994 Oct;26(1-2):242-8. doi: 10.1016/0169-328x(94)90096-5.
Postnatal handling alters hypothalamic-pituitary-adrenal (HPA) responses to stress in the rat. Handling also increases hippocampal glucocorticoid receptor density, and this effect appears to form, in part at least, the basis for the effect of handling on HPA responsiveness to stress. In the present study we have used in situ hybridization techniques to examine the effect of postnatal handling on the expression of glucocorticoid and mineralocorticoid receptor mRNAs in various cell fields of the dorsal hippocampus in adult rats. Grain counting analysis over individual cells showed that postnatal handling significantly increased (40-50%) glucocorticoid receptor mRNA in all hippocampal cell fields. In contrast, handling had no effect on mineralocorticoid receptor mRNA expression. These findings are consistent with the results of receptor binding studies showing that handling increases hippocampal glucocorticoid receptor, but not mineralocorticoid receptor density. Thus, the increase in glucocorticoid receptor binding in handled animals is likely associated with altered rates of receptor biosynthesis. Moreover, the handling effect is quite specific, altering glucocorticoid receptor, but not mineralocorticoid receptor mRNA expression. The mechanism(s) whereby glucocorticoid receptor gene expression is permanently increased by postnatal handling remains to be determined.
出生后处理会改变大鼠下丘脑-垂体-肾上腺（HPA）对应激的反应。处理还会增加海马糖皮质激素受体密度，并且这种效应似乎至少部分地构成了处理对HPA对应激反应性产生影响的基础。在本研究中，我们使用原位杂交技术来检测出生后处理对成年大鼠背侧海马不同细胞区域中糖皮质激素和盐皮质激素受体mRNA表达的影响。对单个细胞进行颗粒计数分析表明，出生后处理显著增加了所有海马细胞区域中糖皮质激素受体mRNA的表达（增加40 - 50%）。相比之下，处理对盐皮质激素受体mRNA表达没有影响。这些发现与受体结合研究的结果一致，即处理增加了海马糖皮质激素受体密度，但没有增加盐皮质激素受体密度。因此，在经过处理的动物中糖皮质激素受体结合的增加可能与受体生物合成速率的改变有关。此外，处理效应具有相当的特异性，改变了糖皮质激素受体mRNA的表达，但没有改变盐皮质激素受体mRNA的表达。出生后处理使糖皮质激素受体基因表达永久性增加的机制仍有待确定。
