title: Gonadotropin-releasing hormone agonist selectively augments thymopoiesis and prevents cell apoptosis in LPS induced thymic atrophy model independent of gonadal steroids.
abstract: Lipopolysaccharide (LPS) causes acute thymic atrophy, a phenomenon that has been linked to immune dysfunction and poor survival during sepsis. The systemic response to LPS involves a rise in glucocorticoids and proinflammatory cytokines which contribute greatly to thymic involution and apoptosis. Gonadotropin-releasing hormone (GnRH) analog exerts thymopoietic regulatory effects and possesses immunostimulant properties. We determined whether leuprolide, a GnRH analog can be useful in LPS induced thymic involution and apoptosis. Mice injected with 100 μg of LPS intraperitoneally led to involution of thymus, to decrease of CD4(+)8(+) thymocyte subset, and to fragmentation of thymic DNA. Leuprolide (100 μg/mouse, s.c.) pretreatment significantly attenuated LPS induced thymic atrophy, and also reduced LPS induced systemic rise in corticosterone levels. The observed effect of leuprolide remained unaffected in castrated and ovariectomized mice. Collectively, leuprolide has protective action independent of gonadal steroids, which was mediated by blunting of the systemic corticosteroid response in LPS induced thymic atrophy model.
authors.affiliation: University Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Mahatma Jyotiba Fuley Shaikshanik Parisar, Amravati Road, Nagpur, 440 033 MS, India.
authors.forename: Meenal P
authors.initials: MP
authors.lastname: Ullewar
authors.affiliation: Kamla Nehru College of Pharmacy, Borkhedi Gate, Near Railway Crossing, Butibori, Nagpur, 441108 MS, India. Electronic address: umathesn@hotmail.com.
authors.forename: Sudhir N
authors.initials: SN
authors.lastname: Umathe
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001284:Atrophy / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D002369:Castration; D003345:Corticosterone / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D042341:Gonadal Hormones / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000378:metabolism; D038041:Lymphopoiesis / Q000187:drug effects; D008297:Male; D051379:Mice; D010052:Ovariectomy; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D013950:Thymus Gland / Q000187:drug effects* / Q000473:pathology*
chemical_list: D042341:Gonadal Hormones; D008070:Lipopolysaccharides; D007987:Gonadotropin-Releasing Hormone; D016729:Leuprolide; D003345:Corticosterone
keywords: Apoptosis; Corticotrophin-releasing factor; Gonadotropin-releasing hormone; Lipopolysaccharide; Thymocytes