IMMUNOCYTOCHEMICAL LOCATION AND HORMONAL-CONTROL OF ANDROGEN RECEPTORS IN LACRIMAL TISSUES OF THE FEMALE MRL MP-LPR/LPR MOUSE MODEL OF SJOGRENS-SYNDROME/

Androgen therapy suppresses lymphocyte infiltration in, and improves t he functional activity of, lacrimal glands in a female mouse model (MR L/Mp-lpr/lpr [MRL/lpr]) of Sjogren's syndrome. To extend these finding s, the current investigation was designed to identify the cellular tar get(s) within lacrimal tissue that may mediate this androgen effect. I n addition, we explored the endocrine regulation of androgen receptors in autoimmune lacrimal glands. Adult, female MRL/lpr mice were expose d systemically to vehicle, steroid hormones or immunosuppressive agent s for varying time intervals after the onset of disease. Immediately b efore or after treatment, lacrimal glands were obtained and processed to determine the cellular distribution and nuclear density of androgen receptors by immunoperoxidase and image analysis techniques, Our find ings demonstrated that: (1) androgen receptors exist almost exclusivel y within nuclei of acinar and ductal epithelial cells in lacrimal tiss ue of MRL/lpr mice; (2) androgen receptors are not detectable in the e xtensive lymphocytic populations that infiltrate the gland; (3) testos terone administration induces a significant increase in the number of androgen receptor-containing cells in, as well as the density of andro gen receptors in epithelial cell nuclei of, lacrimal tissue; (4) hormo ne action is steroid-specific: administration of androgen analogues, b ut not estrogens, glucocorticoids or cyclophosphamide, stimulate the a ccumulation of androgen receptors; and (5) androgen receptor density i s significantly reduced following the withdrawal of androgen therapy. These results show that epithelial cells, but not lymphocytes, are the androgen target cells in lacrimal tissue, and suggest that these cell s may mediate the androgen-related immunosuppression and functional en hancement in lacrimal glands of autoimmune female mice. Our findings a lso demonstrate that androgens increase the expression of their own re ceptors in MRL/lpr lacrimal tissue. (C) 1995 Academic Press Limited