Mellström B, Naranjo J R, Santos A, Gonzalez A M, Bernal J
Instituto de Investigaciones Biomédicas, Consejo Superior Investigaciones Científicas Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
Mol Endocrinol. 1991 Sep;5(9):1339-50. doi: 10.1210/mend-5-9-1339.
Thyroid hormone is important for normal brain development. Cellular responses to thyroid hormone are mediated by multiple nuclear receptors, classified into alpha- and beta-subtypes. In the rat, expression of both the alpha and beta genes results in several translation products. By using cRNA probes common to alpha transcripts or specific for alpha-1 and beta-1, we have studied the distribution of these transcripts in rat brain at different stages of development from embryonic day 14 to adult age by using in situ hybridization histochemistry. On embryonic day 14, the alpha-1 mRNA is already widely expressed at a low level in the developing brain. The alpha-1 mRNA is developmentally regulated and showed a peak in expression during the first 3 postnatal weeks in the cerebral cortex, amygdala, hippocampus, and cerebellum. The probe common to the alpha transcripts detected a widespread distribution and high levels of these forms in the same regions throughout postnatal development. The level of beta-1 mRNA before birth was low or undetectable. The beta-1 transcript showed developmental regulation as well, with a high level at birth in the mitral cell layer of the olfactory bulb, accumbens nucleus, caudate, and hippocampal field CA1 and increasing levels in other regions later during development. Complementary expression of the alpha and beta forms was seen in the cerebral cortex and hippocampus. The differential temporal and spatial distribution as well as coexpression at comparable levels in certain brain regions suggest different roles for the c-erbA proteins during brain development and in the mature animal.
甲状腺激素对正常脑发育至关重要。细胞对甲状腺激素的反应由多种核受体介导，这些核受体分为α和β亚型。在大鼠中，α和β基因的表达产生几种翻译产物。通过使用α转录本共有的或对α-1和β-1特异的cRNA探针，我们利用原位杂交组织化学研究了从胚胎第14天到成年期不同发育阶段大鼠脑中这些转录本的分布。在胚胎第14天，α-1 mRNA已在发育中的脑中低水平广泛表达。α-1 mRNA受到发育调控，在出生后的前3周在大脑皮层、杏仁核、海马体和小脑中表达达到峰值。α转录本共有的探针在整个出生后发育过程中在相同区域检测到这些形式的广泛分布和高水平表达。出生前β-1 mRNA水平低或无法检测到。β-1转录本也表现出发育调控，出生时在嗅球的僧帽细胞层、伏隔核、尾状核和海马场CA1中水平较高，在发育后期其他区域水平升高。在大脑皮层和海马体中观察到α和β形式的互补表达。不同的时空分布以及在某些脑区相当水平的共表达表明c-erbA蛋白在脑发育过程中和成熟动物中具有不同的作用。
