Differential ligand selectivity of androgen receptors α and ß from Murray-Darling rainbowfish (Melanotaenia fluviatilis).
Gen Comp Endocrinol
; 212: 84-91, 2015 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-25644213
ABSTRACT
Androgen receptors (ARs) mediate the physiological effects of androgens in vertebrates. In fishes, AR-mediated pathways can be modulated by aquatic contaminants, resulting in the masculinisation of female fish or diminished secondary sex characteristics in males. The Murray-Darling rainbowfish (Melanotaenia fluviatilis) is a small-bodied freshwater teleost used in Australia as a test species for environmental toxicology research. We determined concentration-response profiles for selected agonists and antagonists of rainbowfish ARα and ARß using transient transactivation assays. For both ARα and ARß, the order of potency of natural agonists was 11-ketotestosterone (11-KT)>5α-dihydrotestosterone>testosterone>androstenedione. Methyltestosterone was a highly potent agonist of both receptors relative to 11-KT. The relative potency of the veterinary growth-promoting androgen, 17ß-trenbolone, varied by more than a factor of 5 between ARα and ARß. The non-steroidal anti-androgen bicalutamide exhibited high inhibitory potency relative to the structurally related model anti-androgen, flutamide. The inhibitory potency of the agricultural fungicide, vinclozolin, was approximately 1.7-fold relative to flutamide for ARα, but over 20-fold in the case of ARß. Fluorescent protein tagging of ARs showed that the rainbowfish ARα subtype is constitutively localised to the nucleus, while ARß is cytoplasmic in the absence of ligand, an observation which agrees with the reported subcellular localisation of AR subtypes from other teleost species. Collectively, these data suggest that M. fluviatilis ARα and ARß respond differently to environmental AR modulators and that in vivo sensitivity to contaminants may depend on the tissue distribution of the AR subtypes at the time of exposure.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Androgênicos
/
Peixes
/
Antagonistas de Androgênios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
País/Região como assunto:
Oceania
Idioma:
En
Revista:
Gen Comp Endocrinol
Ano de publicação:
2015
Tipo de documento:
Article