Testing androgen‐induced immunosuppression: Environmental androgens as a model system for steroid‐immune interaction

• Published in: Journal of experimental zoology. Part A, Ecological and integrative physiology Vol. 341; no. 4; pp. 431 - 439
• Main Authors: López‐Pérez, Jorge E., Goessling, Jeffrey M., Murray, Christopher M.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-05-2024
• Subjects: acquired immunity; Alligators; Alligators and Crocodiles; Androgens; Androgens - pharmacology; Animals; Antibodies; Antigens; Aquatic animals; Aquatic reptiles; Crocodylia; ecoimmunology; endocrine disrupting compounds; Exposure; Female; Gonads; Haemolysis; Hemagglutination; Hormones; Humans; Humoral immunity; Hypotheses; Immune response; Immunity; Immunocompetence; Immunosuppression; Immunosuppression Therapy; In vivo methods and tests; innate immunity; Methyltestosterone; Methyltestosterone - pharmacology; Physiological effects; Physiology; Sex hormones; Steroids; acquired immunity; endocrine disrupting compounds; methyltestosterone; innate immunity; ecoimmunology
• ISSN: 2471-5638; 2471-5646
• DOI: 10.1002/jez.2795

It is well known that hormones influence and direct most facets of physiology; however, there is still contention regarding the directions of certain relationships, for example, between gonadal hormones and immunity. Among the many proposed relationships relating to gonadal–immune interactions, support for immunosuppressive effects of androgens remains prominent within physiological literature. Although ample study has been directed toward the immunosuppressive effects of androgens, considerable disagreement remains regarding their influence on immune function. In this study, we test the hypothesis that androgens inhibit immunocompetence in the American alligator (Alligator mississippiensis). Developing alligators were incubated at female‐producing temperatures with a subset of individuals being exposed to 17‐α‐methyltestosterone (MT) before sexual determination. 17‐α‐methyltestosterone is a potent androgen, not aromatizable by crocodilians, that has been found to exert masculinizing effects in exposed crocodilian populations in vivo and in vitro. Additionally, a subset of animals was exposed to a novel antigen to quantify innate and acquired immune function. We recovered no significant differences in leukocyte ratios or proportions between groups and found no significant differences in innate immune function as measured by hemolysis‐hemagglutination. However, we did find significant differences in acquired immune function, where masculinized individuals expressed greater antibody titers. Our findings reject the hypothesis that androgens suppress immune function; rather, androgens may be immunoenhancing to acquired humoral responses and neutral to innate humoral immunity in crocodilians.
We tested the hypothesis that androgens inhibit immunocompetence via the masculinization of female alligators using 17‐α‐methyltestosterone, a potent exogenous androgen. Our findings reject the hypothesis that androgens suppress immune function; rather, androgens may be immunoenhancing to acquired humoral responses and neutral to innate humoral immunity in crocodilians.