CLINICAL IMMUNOLOGY .ANl) lMMUNOI’A7HOI.OGY 36, io- 17 (1985) Effects of Testosterone on the Development of Autoimmune Thyroiditis in Two Strains of Chicken’ WILLIAM C.GAUSE ANDJAMES A. MARSH Department of Poultry and Aviun Sciences. Cornell Utlibvrsity. Ithacu. Neu, York 14853 The effect of testosterone on organ-specific spontaneous autoimmune thyroiditis (SAT) was examined in two strains of chicken: the Obese (OS) strain, which develops SAT at several weeks of age and the control Special C (Sp. C) strain. Both were originally selected from the C strain and are homozygous for the B” major histocompatibility haplotype. Testes development and testosterone levels in the OS strain were consider- ably less than those found in comparably aged birds of the Sp. C strain. Testosterone supplementation of the OS strain significantly decreased thyroid infiltration by lympho- cytes while castration of the Sp. C strain significantly enhanced infiltration. These results suggest that testosterone reduces SAT and that the hormonal constitution in both strains of chicken affect the frequency of occurrence and severity of this disorder. o 19x5 Academic Press. Inc. INTRODUCTION Autoimmune pathogenesis is an immune response against self antigens which contributes to or causes disease (1). Generally, it arises due to a lack of tolerance towards self. This tolerance appears to arise early in development, possibly due to the elimination of self-reactive cells in the thymus. Alternatively, there is con- siderable evidence that autoreactive cells, particularly B cells, do persist in the adult (2). Their activity, however, is generally inhibited, possibly by T suppressor cells (3). Autoimmune disorders are more frequent in females than males (4). One ex- planation for this disparity is that testosterone affects the development of the immune system, resulting in decreased activity of autoreactive clones (5). Ex- periments using NZB/NZW mice, which develop an autoimmune disorder similar to human systemic lupus erythematosus, reveal an increased severity of this dis- ease in castrated males compared to the controls (4, 6-8). Conversely, the se- verity is decreased by testosterone supplementation of either males or females (7, 8). More recently, Okayasu et al. (9) have demonstrated that castrated mice exhibiting experimentally induced autoimmune thyroiditis have higher thyroglob- ulin autoantibody (TgAAb) levels than untreated controls, while testosterone treatment results in decreased levels. The experiments discussed here examine the effects of testosterone on the development of spontaneous autoimmune thyroiditis (SAT) in the Obese (OS) strain of chicken, one of the few experimental models for spontaneous organ- ’ These studies were supported in part by Projects NY(C)157431 and NY(Qt.57435. 10 0090- 1229/85 $1.50 Copyright 8 1985 by Academic Press. Inc All rights of reproduction in any form reserved