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

Medaka (Oryzias latipes) 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...

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Main Authors: Tomoya Uchimura, Seiji Hara, Takashi Yazawa, Yasuhiro Kamei, Takeshi Kitano
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-08-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fendo.2019.00529/full
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author Tomoya Uchimura
Seiji Hara
Takashi Yazawa
Yasuhiro Kamei
Takeshi Kitano
author_facet Tomoya Uchimura
Seiji Hara
Takashi Yazawa
Yasuhiro Kamei
Takeshi Kitano
author_sort Tomoya Uchimura
collection DOAJ
description Medaka (Oryzias latipes) 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 crh paralogs, named crha and crhb, have been identified. Recently, the expression of crhb but not crha 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 crhb is involved in masculinization induced by HT. However, the transcriptional regulation of crhb 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 hsp70.1 and hsp30, were increased. Overexpression of hsp70.1 or hsp30 in cultured rat hypothalamic 4B cells significantly induced crh gene expression. Moreover, hypothalamic hsp70.1-overexpressing transgenic medaka also showed increased crhb 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 crhb gene expression in the hypothalamus.
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spelling doaj.art-003dc796049142d3967f471ce2c7f7152022-12-21T19:50:32ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922019-08-011010.3389/fendo.2019.00529473543Involvement of Heat Shock Proteins on the Transcriptional Regulation of Corticotropin-Releasing Hormone in MedakaTomoya Uchimura0Seiji Hara1Takashi Yazawa2Yasuhiro Kamei3Takeshi Kitano4Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kumamoto, JapanDepartment of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kumamoto, JapanDepartment of Biochemistry, Asahikawa Medical University, Asahikawa, JapanSpectrography and Bioimaging Facility, National Institute for Basic Biology Core Research Facilities, National Institute for Basic Biology, Okazaki, JapanDepartment of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kumamoto, JapanMedaka (Oryzias latipes) 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 crh paralogs, named crha and crhb, have been identified. Recently, the expression of crhb but not crha 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 crhb is involved in masculinization induced by HT. However, the transcriptional regulation of crhb 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 hsp70.1 and hsp30, were increased. Overexpression of hsp70.1 or hsp30 in cultured rat hypothalamic 4B cells significantly induced crh gene expression. Moreover, hypothalamic hsp70.1-overexpressing transgenic medaka also showed increased crhb 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 crhb gene expression in the hypothalamus.https://www.frontiersin.org/article/10.3389/fendo.2019.00529/fullcorticotropin-releasing hormonecortisolheat shock proteinhypothalamusmedakasex determination
spellingShingle Tomoya Uchimura
Seiji Hara
Takashi Yazawa
Yasuhiro Kamei
Takeshi Kitano
Involvement of Heat Shock Proteins on the Transcriptional Regulation of Corticotropin-Releasing Hormone in Medaka
Frontiers in Endocrinology
corticotropin-releasing hormone
cortisol
heat shock protein
hypothalamus
medaka
sex determination
title Involvement of Heat Shock Proteins on the Transcriptional Regulation of Corticotropin-Releasing Hormone in Medaka
title_full Involvement of Heat Shock Proteins on the Transcriptional Regulation of Corticotropin-Releasing Hormone in Medaka
title_fullStr Involvement of Heat Shock Proteins on the Transcriptional Regulation of Corticotropin-Releasing Hormone in Medaka
title_full_unstemmed Involvement of Heat Shock Proteins on the Transcriptional Regulation of Corticotropin-Releasing Hormone in Medaka
title_short Involvement of Heat Shock Proteins on the Transcriptional Regulation of Corticotropin-Releasing Hormone in Medaka
title_sort involvement of heat shock proteins on the transcriptional regulation of corticotropin releasing hormone in medaka
topic corticotropin-releasing hormone
cortisol
heat shock protein
hypothalamus
medaka
sex determination
url https://www.frontiersin.org/article/10.3389/fendo.2019.00529/full
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