INFLUENCE OF GENDER AND THE ENDOCRINE ENVIRONMENT ON THE DISTRIBUTIONOF ANDROGEN RECEPTORS IN THE LACRIMAL GLAND

Androgens are known to regulate both the structure and function of lac rimal tissue in a variety of species. To explore the endocrine basis f or this hormone action, the following study was designed to: (1) deter mine the cellular distribution of androgen receptors in the lacrimal g land; and (2) examine the influence of gender and the endocrine enviro nment on the glandular content of these binding sites. Lacrimal glands were obtained from intact, castrated, hypophysectomized, diabetic or sham-operated male or female adult rats, mice or hamsters, as well as from orchiectomized rats exposed to placebo compounds or physiological levels of testosterone. The cellular location of androgen receptors w as evaluated by utilizing an immunoperoxidase protocol, in which a pur ified rabbit polyclonal antibody to the rat androgen receptor was used as the first antibody. Our findings with lacrimal glands showed that: (1) androgen receptors are located almost exclusively in nuclei of ep ithelial cells; (2) the cellular distribution or intranuclear density of these binding sites is far more extensive in glands of males, as co mpared to females; (3) orchiectomy or hypophysectomy, but not sham-sur gery or diabetes, lead to a dramatic reduction in the immunocytochemic al expression of androgen receptors; and (4) testosterone administrati on to orchiectomized rats induces a marked increase in androgen recept or content, relative to that in placebo-exposed glands. Our results al so reveal that a 10 kb androgen receptor mRNA exists in the rat lacrim al gland. Overall, these findings demonstrate that gender and the endo crine system may significantly influence the distribution of androgen binding sites in rat lacrimal tissue. Moreover, our results show that androgens up-regulate their own lacrimal gland receptors.