Leptin-Mediated Modulation of Steroidogenic Gene Expression in Hypoxic Zebrafish Embryos: Implications for the Disruption of Sex Steroids

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• 作者：Richard Man Kit Yu ; Daniel Ling Ho Chu ; Tian-feng Tan ; Vincent Wai Tsun Li ; Alice Ka Yee Chan ; John P. Giesy ; Shuk Han Cheng ; Rudolf Shiu Sun Wu ; Richard Yuen Chong Kong
• 刊名：Environmental Science & Technology (ES&T)
• 出版年：2012
• 出版时间：August 21, 2012
• 年：2012
• 卷：46
• 期：16
• 页码：9112-9119
• 全文大小：336K
• 年卷期：v.46,no.16(August 21, 2012)
• ISSN：1520-5851

文摘

Hypoxia can impair reproduction of fishes through the disruption of sex steroids. Here, using zebrafish (Danio rerio) embryos, we investigated (i) whether hypoxia can directly affect steroidogenesis independent of pituitary regulation via modulation of steroidogenic gene expression, and (ii) the role of leptin in hypoxia-induced disruption of steroidogenesis. Exposure of fertilized zebrafish embryos to hypoxia (1.0 mg O₂ L^鈥?) from 0鈥?2 h postfertilization (hpf), a developmental window when steroidogenesis is unregulated by pituitary influence, resulted in the up-regulation of cyp11a, cyp17, and 3尾-hsd and the down-regulation of cyp19a. Similar gene expression patterns were observed for embryos exposed to 10 mM cobalt chloride (CoCl₂, a chemical inducer of hypoxia-inducible factor 1, HIF-1), suggesting a regulatory role of HIF-1 in steroidogenesis. Testosterone (T) and estradiol (E2) concentrations in hypoxic embryos were greater and lesser, respectively, relative to the normoxic control, thus leading to an increased T/E2 ratio. Expression of the leptin-a gene (zlep-a) was up-regulated upon both hypoxia and CoCl₂ treatments. Functional assays suggested that under hypoxia, elevated zlep-a expression might activate cyp11a and 3尾-hsd and inhibit cyp19a. Overall, this study indicates that hypoxia, possibly via HIF-1-induced leptin expression, modulates sex steroid synthesis by acting directly on steroidogenic gene expression.