Gonadotropin-releasing hormone agonist influences absolute levels of lymphocyte subsets in vivo in male mice

Our earlier studies have demonstrated that gonadotropin-releasing hormone (GnRH) agonists suppress immune system function in female mice. No systematic studies regarding the effect of gender on immune system function following GnRH agonist treatment, however, have been reported. This study. therefore, investigated sequential changes in lymphocyte subsets in 3- and 10-week-old male mice following agonist or placebo administration. Changes in immunophenotypic expression of lymphocytes from thymus, bone marrow, spleen, and blood were analysed at periodic intervals. Upon agonist administration, plasma testosterone levels were significantly increased in pre-pubertal mice, but were significantly decreased in post-pubertal males. Absolute thymic weights, thymocytes and T subsets were significantly increased from the third week regardless of gonadal status. Blood lymphocyte subsets showed a decreasing trend after agonist administration in pre-pubertal males, whereas no differences were observed in post-pubertal males. No significant differences were observed in spleen cells after agonist administration. These studies, together with earlier observations in female mice indicate that GnRH agonist effects on the immune system, are independent of steroid hormone levels. In contrast to suppressive effects in females, GnRH agonists induce no change or ultimately enhanced lymphocyte counts in males, indicating differential effects on the immune system between males and females. This may have important implications for the treatment of various diseases.