ZFIN ID: ZDB-PUB-090112-13
Androgens Upregulate cyp19a1b (Aromatase B) Gene Expression in the Brain of Zebrafish (Danio rerio) Through Estrogen Receptors
Mouriec, K., Gueguen, M.M., Manuel, C., Percevault, F., Thieulant, M.L., Pakdel, F., and Kah, O.
Date: 2009
Source: Biology of reproduction   80(5): 889-896 (Journal)
Registered Authors: Kah, Olivier
Keywords: androgen receptor, aromatase, beta-diol, brain, central nervous system, cyp19a1b, dihydrotestosterone, estradiol, estradiol receptor, radial glial cell, testosterone, zebrafish
MeSH Terms:
  • Androgens/metabolism
  • Androgens/pharmacology*
  • Animals
  • Aromatase/genetics*
  • Aromatase/metabolism
  • Base Sequence
  • Brain/drug effects*
  • Brain/metabolism*
  • Cell Line
  • Dihydrotestosterone/metabolism
  • Dihydrotestosterone/pharmacology
  • Genes, Reporter
  • Humans
  • Larva/drug effects
  • Larva/metabolism
  • Luciferases/genetics
  • Neuroglia/drug effects
  • Neuroglia/metabolism
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Receptors, Androgen/genetics
  • Receptors, Androgen/metabolism
  • Receptors, Estrogen/metabolism*
  • Recombinant Proteins/genetics
  • Recombinant Proteins/metabolism
  • Testosterone/metabolism
  • Testosterone/pharmacology
  • Transfection
  • Up-Regulation/drug effects
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed: 19129512 Full text @ Biol. Reprod.
ABSTRACT
The brain of teleosts is known for its strong aromatase expression, exhibiting unique features compared to other vertebrates. Among these features is the high sensitivity of aromatase B (the product of cyp19a1b) to estrogens. This effect involves the binding of estrogen receptors on an estrogen-responsive element (ERE) of the cyp19a1b promoter. Given the presence of potential androgen-responsive elements (ARE) on this promoter, in vivo and in vitro effects of androgens were studied. The brain of teleosts is known for its strong aromatase expression, exhibiting unique features compared to other vertebrates. Among these features is the high sensitivity of aromatase B (the product of cyp19a1b) to estrogens. This effect involves the binding of estrogen receptors on an estrogen-responsive element (ERE) of the cyp19a1b promoter. Given the presence of potential androgen-responsive elements (ARE) on this promoter, in vivo and in vitro effects of androgens were studied. Using immunohistochemistry and quantitative PCR on zebrafish embryos, we found that cyp19a1b is up-regulated by testosterone, an aromatizable androgen, and by 5alpha-dihydrotestosterone, a non-aromatizable androgen, suggesting a potential androgenic regulation of cyp19a1b through androgen receptors. To assess a putative direct regulation of the cyp19a1b gene by androgen receptors (AR), we transfected U-251MG cells with zebrafish ar together with a luciferase reporter gene driven by 3000 bp of the proximal cyp19a1b promoter, containing the ERE and potential ARE. Interestingly, although zebrafish ar activated luciferase reporter genes controlled by ARE, they failed to induce the cyp19a1b-luciferase construct. This data suggests that the androgenic regulation of cyp19a1b does not involve AR. We further showed that regulation of the cyp19a1b gene by testosterone is in fact due to aromatization, whilst the effect of 5alpha-dihydrotestosterone (DHT) involves conversion into 5alpha-androstane-3beta, 17beta-diol (betadiol), a metabolite of DHT with known estrogenic activity. The blockage of the androgen regulation of cyp19a1b expression using anti-estrogens further confirmed the involvement of estrogen receptors in mediating these effects.
ADDITIONAL INFORMATION