- Title
- Overexpression and knockdown of hypoxia-inducible factor 1 disrupt the expression of steroidogenic enzyme genes and early embryonic development in zebrafish
- Creator
- Tan, Tianfeng; Yu, Richard Man Kit; Wu, Rudolf Shiu Sun; Kong, Richard Yuen Chong
- Relation
- Gene Regulation and Systems Biology Vol. 11, p. 1-11
- Publisher Link
- http://dx.doi.org/10.1177/1177625017713193
- Publisher
- Sage
- Resource Type
- journal article
- Date
- 2017
- Description
- Hypoxia is an important environmental stressor leading to endocrine disruption and reproductive impairment in fish. Although the hypoxia-inducible factor 1 (HIF-1) is known to regulate the transcription of various genes mediating oxygen homeostasis, its role in modulating steroidogenesis-related gene expression remains poorly understood. In this study, the regulatory effect of HIF-1 on the expression of 9 steroidogenic enzyme genes was investigated in zebrafish embryos using a "gain-of-function and loss-of-function" approach. Eight of the genes, CYP11a, CYP11b2, 3β-HSD, HMGCR, CYP17a1, 17β-HSD2, CYP19a, and CYP19b, were found to be differentially upregulated at 24 and 48hpf following zHIF-1α-ΔODD overexpression (a mutant zebrafish HIF-1α protein with proline-414 and proline-557 deleted). Knockdown of zHIF-1α also affected the expression pattern of the steroidogenic enzyme genes. Overexpression of zHIF-1α and hypoxia exposure resulted in downregulated StAR expression but upregulated CYP11a and 3β-HSD expression in zebrafish embryos. Conversely, the expression patterns of these 3 genes were reversed in embryos in which zHIF-1α was knocked down under normoxia, suggesting that these 3 genes are regulated by HIF-1. Overall, the findings from this study indicate that HIF-1-mediated mechanisms are likely involved in the regulation of specific steroidogenic genes.
- Subject
- HIF-1; hypoxia; steroidogenic enzyme genes; zebrafish; steroid hormones
- Identifier
- http://hdl.handle.net/1959.13/1398539
- Identifier
- uon:34448
- Identifier
- ISSN:1177-6250
- Language
- eng
- Full Text
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