title: Modulation of the expression of murine lupus by gonadotropin-releasing hormone analogs.
abstract: 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.
authors.affiliation: Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: J D
authors.initials: JD
authors.lastname: Jacobson
authors.forename: B C
authors.initials: BC
authors.lastname: Nisula
authors.forename: A D
authors.initials: AD
authors.lastname: Steinberg
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D006417:Hematuria; D007074:Immunoglobulin G / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009842:Oligopeptides / Q000627:therapeutic use; D009919:Orchiectomy; D010052:Ovariectomy; D011507:Proteinuria
chemical_list: D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; C057805:LHRH, N-Ac-2-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Arg(5)-Glu(6)-AlaNH2(10)-; D009842:Oligopeptides; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone; C057022:iturelix