Disruption of classical estrogenic targets in brown trout primary hepatocytes by the model androgens testosterone and dihydrotestosterone

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Lopes, C (Author) Other; Madureira, TV (Author) Other; goncalves, j (Author) ICBAS; rocha, e (Author) ICBAS

Journal

Title: Aquatic Toxicology

Vol. 227

ISSN: 0166-445X

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 3 Citations

Other information

Authenticus ID: P-00S-NJD

DOI: 10.1016/j.aquatox.2020.105586

Abstract (EN): Estrogenic effects triggered by androgens have been previously shown in a few studies. Aromatization and direct binding to estrogen receptors (ERs) are the most proposed mechanisms. For example, previously, a modulation of vitellogenin A (VtgA) by testosterone (T), an aromatizable androgen, was reported in brown trout primary hepatocytes. The effect was reversed by an ER antagonist. In this study, using the same model the disruption caused by T and by the non-aromatizable androgen - dihydrotestosterone (DHT), was assessed in selected estrogenic targets. Hepatocytes were exposed (96 h) to six concentrations of each androgen. The estrogenic targets were VtgA, ER alpha, ER beta 1 and two zona pellucida genes, ZP2.5 and ZP3a.2. The aromatase CYP19a1 gene and the androgen receptor (AR) were also included. Modulation of estrogenic targets was studied by quantitative realtime PCR and immunohistochemistry, using an HScore system. VtgA and ER alpha were up-regulated by DHT (1, 10, 100 mu M) and T (10, 100 mu M). In contrast, ER beta 1 was down-regulated by DHT (10, 100 mu M), and T (100 mu M). ZP2.5 mRNA levels were increased by DHT and T (1, 10, 100 mu M), while ZP3a.2 was up-regulated by DHT (100 mu M) and T (10, 100 mu M). Positive correlations were found between VtgA and ER alpha mRNA levels and ZPs and ER alpha, after exposure to both androgens. The mRNA levels of CYP19a1 were not changed, while AR expression tended to increase after micromolar DHT exposures. HScores for Vtg and ZPs corroborated the molecular findings. Both androgens triggered estrogen signaling through direct binding to ERs, most probably ER alpha.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11