Uchimura Tomoya, Hara Seiji, Yazawa Takashi, Kamei Yasuhiro, Kitano Takeshi
Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kumamoto, Japan.
Department of Biochemistry, Asahikawa Medical University, Asahikawa, Japan.
Front Endocrinol (Lausanne). 2019 Aug 2;10:529. doi: 10.3389/fendo.2019.00529. eCollection 2019.
Medaka () are teleost fish with a XX/XY sex determination system. Recently, it was reported that high temperature (HT) induced the masculinization of XX medaka by increasing the levels of cortisol, a major glucocorticoid produced by interrenal cells in teleosts. Cortisol secretion is regulated by adrenocorticotropic hormone (ACTH) secreted from the pituitary gland, which is partly regulated by corticotropin-releasing hormone (CRH) secreted from the hypothalamus. In teleosts, two paralogs, named and , have been identified. Recently, the expression of but not was upregulated by HT during gonadal sex differentiation period in medaka and loss-of-functions of its receptors under HT suppressed masculinization of XX medaka and increase of cortisol levels, suggesting that is involved in masculinization induced by HT. However, the transcriptional regulation of under HT has not been elucidated. We analyzed the gene expression pattern in the hypothalamus of medaka embryos incubated under HT using DNA microarray. The expressions of heat shock protein (hsp) genes, such as and , were increased. Overexpression of or in cultured rat hypothalamic 4B cells significantly induced gene expression. Moreover, hypothalamic -overexpressing transgenic medaka also showed increased gene expression that increased cortisol levels compared with fish incubated at a normal temperature. These results provide the first evidence that HSPs induce cortisol levels by elevating gene expression in the hypothalamus.
青鳉是具有XX/XY性别决定系统的硬骨鱼。最近有报道称，高温（HT）通过提高皮质醇水平诱导XX青鳉雄性化，皮质醇是硬骨鱼肾间细胞产生的主要糖皮质激素。皮质醇的分泌受垂体分泌的促肾上腺皮质激素（ACTH）调节，而ACTH部分受下丘脑分泌的促肾上腺皮质激素释放激素（CRH）调节。在硬骨鱼中，已鉴定出两个旁系同源物，分别命名为 和 。最近，在青鳉性腺性别分化期，高温上调了 的表达，而非 的表达，并且高温下其受体功能丧失抑制了XX青鳉的雄性化和皮质醇水平的升高，这表明 参与了高温诱导的雄性化过程。然而，高温下 的转录调控尚未阐明。我们使用DNA微阵列分析了在高温下孵育的青鳉胚胎下丘脑的基因表达模式。热休克蛋白（hsp）基因如 和 的表达增加。在培养的大鼠下丘脑4B细胞中过表达 或 可显著诱导 基因表达。此外，下丘脑过表达 的转基因青鳉与在正常温度下孵育的鱼相比，也表现出 基因表达增加，皮质醇水平升高。这些结果首次证明热休克蛋白通过提高下丘脑 基因表达来诱导皮质醇水平。
