Fish granulocytes express a constitutively active androgen receptor variant

• A constitutively active AR variant, ARΔLBD, was identified in gilthead seabream.
• ARΔLBD expression is regulated by testosterone in reproductive and immune organs.
• ARΔLBD is expressed in granulocytes but not in macrophages.
• ARΔLBD expression is modulated by both testosterone and immune stimuli.
• These results reveal a new mechanism for the regulation of neutrophil biology.

In humans, alternative splicing of androgen receptor (AR) is usually involved in some diseases. However, our knowledge about the presence of AR variants in other species and its importance for immunity is scant. Here, we report the identification of a constitutively active AR variant lacking the ligand-binding domain (LBD), ARΔLBD, in the fish gilthead seabream. ARΔLBD is expressed in the testis and the head-kidney (HK), and its expression varies with the reproductive stage and is correlated with plasma testosterone (T). In addition, ARΔLBD is expressed in acidophilic granulocytes (AGs), which are the functional equivalent of mammalian neutrophils, but not in macrophages, and its expression is modulated by both T and immune stimuli. Notably, AR and ARΔLBD were able to interact, being the activity of AR dominant at all concentrations tested of the ligand. These results reveal a new mechanism for the regulation of neutrophil biology in vertebrates and explain the conflicting results that suggest that androgens are less important than AR in human and mouse neutrophil homeostasis.