AUTHOR=Uchimura Tomoya , Hara Seiji , Yazawa Takashi , Kamei Yasuhiro , Kitano Takeshi 

TITLE=Involvement of Heat Shock Proteins on the Transcriptional Regulation of Corticotropin-Releasing Hormone in Medaka

JOURNAL=Frontiers in Endocrinology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2019.00529

DOI=10.3389/fendo.2019.00529

ISSN=1664-2392

ABSTRACT=<p>Medaka (<italic>Oryzias latipes</italic>) 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 <italic>crh</italic> paralogs, named <italic>crha</italic> and <italic>crhb</italic>, have been identified. Recently, the expression of <italic>crhb</italic> but not <italic>crha</italic> 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 <italic>crhb</italic> is involved in masculinization induced by HT. However, the transcriptional regulation of <italic>crhb</italic> 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 <italic>hsp70.1</italic> and <italic>hsp30</italic>, were increased. Overexpression of <italic>hsp70.1</italic> or <italic>hsp30</italic> in cultured rat hypothalamic 4B cells significantly induced <italic>crh</italic> gene expression. Moreover, hypothalamic <italic>hsp70.1</italic>-overexpressing transgenic medaka also showed increased <italic>crhb</italic> 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 <italic>crhb</italic> gene expression in the hypothalamus.</p>