Fish granulocytes express a constitutively active androgen receptor variant

Area of Science:

• Comparative immunology
• Endocrinology
• Molecular biology

Background:

• Alternative splicing of androgen receptor (AR) is linked to human diseases.
• The presence and function of AR variants in non-mammalian species, particularly concerning immunity, are poorly understood.

Purpose of the Study:

• To identify and characterize AR variants in fish.
• To investigate the role of AR variants in fish immunity and their relationship with androgens.

Main Methods:

• Identification of a novel AR variant lacking the ligand-binding domain (ARΔLBD) in gilthead seabream.
• Analysis of ARΔLBD expression in different tissues (testis, head-kidney) and correlation with reproductive stage and testosterone (T) levels.
• Investigation of ARΔLBD expression in immune cells (acidophilic granulocytes, macrophages) and its modulation by T and immune stimuli.
• Assessment of the interaction between AR and ARΔLBD.

Main Results:

• A constitutively active AR variant, ARΔLBD, was identified in gilthead seabream, expressed in testis and head-kidney, with levels varying by reproductive stage and correlated with testosterone.
• ARΔLBD is present in acidophilic granulocytes (AGs), the fish equivalent of neutrophils, but not macrophages, and its expression is influenced by testosterone and immune challenges.
• AR and ARΔLBD interact, with AR activity being dominant regardless of ligand concentration.

Conclusions:

• The study reveals a novel mechanism regulating neutrophil biology in vertebrates involving AR variants.
• The findings provide a potential explanation for conflicting results regarding the importance of androgens versus AR in neutrophil homeostasis in mammals.