Shughrue P J, Stumpf W E, MacLusky N J, Zielinski J E, Hochberg R B
Department of Cell Biology and Anatomy, University of North Carolina, Chapel Hill 27599.
Endocrinology. 1990 Feb;126(2):1112-24. doi: 10.1210/endo-126-2-1112.
The presence of estrogen receptor cells in postnatal cerebral cortex and their topographical and numerical changes between birth and postweaning were examined. On postnatal days 0, 2, 8, 12, 18, and 25, six mice (three males and three females) were injected sc with 0.25 microgram/100 g BW 11 beta-methoxy-16 alpha-[125I]iodoestradiol [( 125I]MIE2). Two additional males on postnatal day 2 were each sc injected with 250 micrograms/100 g BW 17 beta-estradiol 1 h before radiolabeled ligand to establish the specificity of nuclear label. Two hours after the injection of [125I]MIE2 brains were frozen, and 4-microns sections were thaw-mounted and processed for autoradiography. Autoradiograms were exposed for 1-45 days, and cortical cells with nuclear uptake and retention of [125I]MIE2 were evaluated at the levels of the frontal pole, preoptic area, and central and posterior hypothalamus. At birth, cells with nuclear label were found predominantly in deep cortical layers. Between birth and postnatal day 2, the number of labeled cells increased in deep and intermediate laminae and first appeared in certain superficial regions. By day 8, labeled cells were concentrated in laminae II-VI of the cingulate/paracingulate and suprarhinal cortex. On day 12, labeling in laminae V and VI declined to a few cells, while a concentration of labeled cells remained in laminae II and III of the cingulate/paracingulate and suprarhinal regions. With subsequent development, an attenuation in labeling at all cortical levels was observed. By day 25, a small cluster of labeled cells remained in lamina II and III of the anterior cingulate, paracingulate, and suprarhinal regions, with additional labeled cells scattered throughout the remaining cortex. Competition with unlabeled 17 beta-estradiol reduced nuclear concentration of ligand in all cortical layers and demonstrated the specificity of [125I]MIE2 for the estrogen receptor. These results show the extensive presence of estrogen target cells in the early postnatal cortex and a profound change in topography and number of target cells during the postnatal period. These findings further suggest an important role for estrogen in the development of certain cortical neurons, possibly involving neuronal differentiation, cell positioning, and connectivity.
研究了产后大脑皮质中雌激素受体细胞的存在情况，以及出生至断奶后其在拓扑结构和数量上的变化。在出生后第0、2、8、12、18和25天，给6只小鼠（3只雄性和3只雌性）皮下注射0.25微克/100克体重的11β-甲氧基-16α-[125I]碘雌二醇[（125I）MIE2]。在出生后第2天，另外两只雄性小鼠在注射放射性标记配体前1小时，分别皮下注射250微克/100克体重的17β-雌二醇，以确定核标记的特异性。注射[125I]MIE2两小时后，将大脑冷冻，制作4微米厚的切片，解冻后进行放射自显影处理。放射自显影片曝光1 - 45天，在额叶极、视前区、下丘脑中部和后部水平评估摄取并保留[125I]MIE2的皮质细胞。出生时，有核标记的细胞主要位于皮质深层。在出生至出生后第2天期间，深层和中层有核标记的细胞数量增加，并且首次出现在某些浅层区域。到第8天，有核标记的细胞集中在扣带/旁扣带皮质和鼻上皮质的II - VI层。在第12天，V层和VI层的标记减少到少数细胞，而扣带/旁扣带和鼻上区域的II层和III层仍有集中的有核标记细胞。随着后续发育，观察到所有皮质水平的标记都有所减少。到第25天，前扣带、旁扣带和鼻上区域的II层和III层仍有一小群有核标记的细胞，其余皮质中也有散在的有核标记细胞。与未标记的17β-雌二醇竞争可降低所有皮质层中配体的核浓度，证明了[125I]MIE2对雌激素受体的特异性。这些结果表明产后早期皮质中广泛存在雌激素靶细胞，并且在出生后时期靶细胞的拓扑结构和数量发生了深刻变化。这些发现进一步表明雌激素在某些皮质神经元发育中起重要作用，可能涉及神经元分化、细胞定位和连接。
