Selectivity, specificity and kinetics of the androgen regulation of the ocular secretory immune system

The purpose of the present investigation was to determine the selectivity, specificity and kinetics of the androgen regulation of the ocular secretory immune system. To examine the mucosal selectivity of hormone action, tears, saliva, respiratory and intestinal secretions, urine and serum were collected from orchiectomized rats following four days of treatment with saline or testosterone. Androgen administration significantly increased the tear levels of IgA and free SC. In contrast, this combined hormone response was not duplicated in other mucosal secretions or serum. Consequently, it appears that the androgen control of the ocular secretory immune system is unique to the eye. To evaluate androgenic specificity, orchiectomized rats were treated for four days with saline, testosterone, 5 alpha-androstan-17 beta-o1 ('5 alpha'), 4-estren-7 alpha-methyl-17 beta-o1-3-one ('4-E') or the synthetic analogue, danazol. Results demonstrated that testosterone and '4-E', a potent androgen, both stimulated the accumulation of tear IgA and free SC, compared to amounts in tears of saline-treated controls. The weak androgen '5 alpha' induced a slight rise in tear free SC, but not IgA, levels, whereas danazol had no effect on the ocular secretory immune system. These findings indicate that androgen structure is of critical importance in modulation of mucosal immunity in the eye. Lastly, to assess the kinetics of hormone action on tear IgA and free SC, orchiectomized rats were acutely (0, 1.5, 4, 7, 12, or 24 hours) or chronically (0, 4, 7, 11, 14, or 17 days) exposed to testosterone. Acute androgen exposure for less than 12 hours did not elicit any change in the tear content of IgA or free SC. In comparison, chronic androgen treatment induced a progressive and dramatic rise in the levels of both tear proteins. By 17 days of hormone exposure, the IgA and free SC concentrations in tears had increased by 14- and 18-fold amounts, respectively, relative to amounts in placebo-treated controls. Of interest, the temporal pattern of accumulation of tear IgA and free SC were different. Overall, these results show prolonged, but not abbreviated, exposure to androgens has a profound impact on the IgA and free SC profile in tears.