Endocrine disruptors, aryl hydrocarbon receptor and cortisol secretion

Area of Science:

• Endocrinology
• Toxicology
• Molecular Biology

Background:

• Endocrine disruptors impact various endocrine tissues, including the adrenal cortex due to its lipophilic nature.
• Xenobiotics may induce adrenocortical dysfunction, but their specific effects on adrenal steroidogenesis, particularly via the aryl hydrocarbon receptor (AHR) pathway, are not well understood.

Purpose of the Study:

• To review existing evidence on how AHR ligands affect adrenal steroidogenesis.
• To specifically examine the impact on cortisol secretion.

Main Methods:

• Systematic review of published literature.
• Focus on studies investigating AHR ligands and adrenal steroidogenesis, particularly cortisol production.
• Analysis of data from various experimental models, animal studies, and human observations.

Main Results:

• Short-term AHR ligand exposure typically induces a stress-like corticosteroid response.
• Long-term exposure often leads to diminished responsiveness to stressors.
• Prenatal exposure effects differ based on offspring sex, observed in mice and human cohorts.
• In vitro results vary: reduced cortisol in fish, increased cortisol in murine and human adrenal cells.
• No direct AHR-binding elements found in steroidogenic enzyme promoters, suggesting indirect mechanisms.

Conclusions:

• Evidence supports the significant impact of AHR ligands on adrenocortical function.
• Further research is needed to fully elucidate the mechanisms and consequences of AHR-mediated effects on adrenal steroidogenesis.