Modulation of the expression of murine lupus by gonadotropin-releasing hormone analogs

Recent studies have suggested that hypothalamic and pituitary hormones may directly influence the immune system. One such hormone with immunomodulatory properties is GnRH. We hypothesized that GnRH and/or the gonadotropins might alter the severity of autoimmune disease through mechanisms distinct from their effects on gonadal hormones. This possibility was tested in a murine model of lupus. We assessed disease severity over time in intact and castrated, male and female, lupus-prone (SWR x NZB) F1 hybrid mice during treatment with GnRH agonist, GnRH antagonist, or vehicle. Compared to vehicle administration, GnRH antagonist administration significantly decreased total serum immunoglobulin G and anti-DNA antibodies in castrated male and female mice and significantly improved survival. In contrast, GnRH agonist administration exerted reciprocal effects in castrated mice, leading to early increases in serum anti-DNA and total immunoglobulin G levels. We conclude that GnRH and/or the gonadotropins can modify the expression of murine lupus independently of their regulation of gonadal steroid secretion.