Evrard Henry C, Balthazart Jacques
Research Group in Behavioral Neuroendocrinology, Centre for Cellular and Molecular Neurobiology, University of Liège, B-4020 Liège, Belgium.
J Neurosci. 2004 Aug 18;24(33):7225-9. doi: 10.1523/JNEUROSCI.1638-04.2004.
In addition to exerting genomic actions via nuclear receptors within hours to days, estrogens also regulate neuronal activity much faster (within seconds) by activating neuronal membrane receptors coupled to intracellular second-messenger pathways. To date, the origin of estrogens inducing rapid effects in the brain remains unclear, although it is often ascribed to the gonads. We report here that an acute blockade of the endogenous synthesis of estrogens in the quail spinal dorsal horn markedly reduced, within 1 min, the behavioral responsiveness to a thermal painful stimulus. Similar rapid effects in the opposite direction were induced by estradiol. This finding identifies a new paracrine and nongenomic mechanism for the regulation of pain by estrogens. Such regulation was assumed previously to result only from slow genomic actions of estrogens arising from the ovaries. Also, quite importantly, this finding suggests that the numerous rapid nongenomic effects of estrogens in the CNS could depend on their immediate local production by the enzyme aromatase, independently from the gonads.
除了在数小时至数天内通过核受体发挥基因组作用外，雌激素还可通过激活与细胞内第二信使途径偶联的神经元膜受体更快地（在数秒内）调节神经元活动。迄今为止，尽管雌激素在大脑中诱导快速效应的来源通常归因于性腺，但其起源仍不清楚。我们在此报告，鹌鹑脊髓背角内雌激素内源性合成的急性阻断在1分钟内显著降低了对热痛刺激的行为反应性。雌二醇则诱导了相反方向的类似快速效应。这一发现确定了雌激素调节疼痛的一种新的旁分泌和非基因组机制。此前认为这种调节仅源于卵巢产生的雌激素的缓慢基因组作用。同样非常重要的是，这一发现表明，雌激素在中枢神经系统中的众多快速非基因组效应可能取决于其由芳香化酶立即进行的局部产生，而与性腺无关。
