title: Leptin-mediated modulation of steroidogenic gene expression in hypoxic zebrafish embryos: implications for the disruption of sex steroids.
abstract: 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 O(2) L(-1)) from 0-72 h postfertilization (hpf), a developmental window when steroidogenesis is unregulated by pituitary influence, resulted in the up-regulation of cyp11a, cyp17, and 3β-hsd and the down-regulation of cyp19a. Similar gene expression patterns were observed for embryos exposed to 10 mM cobalt chloride (CoCl(2), 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 CoCl(2) treatments. Functional assays suggested that under hypoxia, elevated zlep-a expression might activate cyp11a and 3β-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.
authors: School of Environmental and Life Sciences, The University of Newcastle, Callaghan, New South Wales, Australia.
authors: Richard Man Kit
authors: RM
authors: Yu
authors: Daniel Ling Ho
authors: DL
authors: Chu
authors: Tian-feng
authors: TF
authors: Tan
authors: Vincent Wai Tsun
authors: VW
authors: Li
authors: Alice Ka Yee
authors: AK
authors: Chan
authors: John P
authors: JP
authors: Giesy
authors: Shuk Han
authors: SH
authors: Cheng
authors: Rudolf Shiu Sun
authors: RS
authors: Wu
authors: Richard Yuen Chong
authors: RY
authors: Kong
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D018507:Gene Expression Regulation, Developmental; D020738:Leptin / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics
chemical_list: D017931:DNA Primers; D020738:Leptin