Yonehara Keisuke, Suzuki Masatoshi, Yamanouchi Keitaro, Nishihara Masugi
Department of Veterinary Physiology, Veterinary Medical Science, The University of Tokyo, Japan.
J Reprod Dev. 2003 Dec;49(6):547-52. doi: 10.1262/jrd.49.547.
Estrogen plays an important role in sexual differentiation of the brain in rats during the perinatal period. To elucidate molecular mechanisms underlying sexual differentiation of the brain, in this study we investigated genes differentially expressed between sexes or induced to express by estrogen in neonatal rat hypothalamus using DNA microarray analysis in combination with real-time RT-PCR. It was found that the levels of expression of the genes encoding glutamic acid decarboxylase 65 and coronin 1b were higher in male than female hypothalamus on postnatal day (PN) 5 and those of collagen type 3 alpha1 and thioredoxin reductase 2 genes in female hypothalamus on PN5 were decreased and increased, respectively, by treatment with estradiol on PN2. Then the developmental changes in the expression of these 4 genes were examined from 1 day before the parturition to PN9, and they all showed sexual dimorphic patterns. In addition, dependence of the expression of these genes on either estradiol, testosterone or dihydrotestosterone during the neonatal period was confirmed. These results suggest that these four genes are involved in sexual differentiation of the rat brain, and that androgen per se as well as estrogen may take part in the processes.
雌激素在围产期大鼠大脑的性别分化中起重要作用。为阐明大脑性别分化的分子机制，在本研究中，我们结合实时逆转录-聚合酶链反应，使用DNA微阵列分析，研究新生大鼠下丘脑性别间差异表达或由雌激素诱导表达的基因。结果发现，出生后第5天雄性下丘脑编码谷氨酸脱羧酶65和冠蛋白1b的基因表达水平高于雌性，而出生后第5天雌性下丘脑的Ⅲ型胶原α1和硫氧还蛋白还原酶2基因表达水平，在出生后第2天经雌二醇处理后分别降低和升高。然后从分娩前1天到出生后第9天检查这4个基因表达的发育变化，它们均呈现出性别二态性模式。此外，证实了这些基因在新生儿期的表达依赖于雌二醇、睾酮或双氢睾酮。这些结果表明，这四个基因参与大鼠大脑的性别分化，雄激素本身以及雌激素可能都参与了这一过程。
