Disruption of classical estrogenic targets in brown trout primary hepatocytes by the model androgens testosterone and dihydrotestosterone
Abstract
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, ERα, ERβ1 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 real-time PCR and immunohistochemistry, using an HScore system. VtgA and ERα were up-regulated by DHT (1, 10, 100 μM) and T (10, 100 μM). In contrast, ERβ1 was down-regulated by DHT (10, 100 μM), and T (100 μM). ZP2.5 mRNA levels were increased by DHT and T (1, 10, 100 μM), while ZP3a.2 was up-regulated by DHT (100 μM) and T (10, 100 μM). Positive correlations were found between VtgA and ERα mRNA levels and ZPs and ERα, 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.…
Read the paper
Related studies
- Induced osteoblast differentiation by amide derivatives of stilbene: The possible osteogenic agents
- On model selections for repeated measurement data in clinical studies
- Regulation of GLUT transporters by flavonoids in androgen-sensitive and -insensitive prostate cancer cells
- Region-specific microRNA signatures in the human epididymis
- Synthesis, biological evaluation and molecular docking of 4-Amino-2H-benzo[h]chromen-2-one (ABO) analogs containing the piperazine moiety
- In Vitro characterization of the endocrine disrupting effects of per- and poly-fluoroalkyl substances (PFASs) on the human androgen receptor
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.