title: Leukemia inhibitory factor signaling is implicated in embrionic development of the HPA axis.
abstract: Leukemia inhibitory factor (LIF) is expressed in the hypothalamic-pituitary adrenal (HPA) axis and stimulates pituitary POMC transcription. The role of LIF receptor signaling in HPA axis development was examined. Lifr -/- and Lifr +/+ fetuses were obtained by Cesarean section on E18.5. Despite a 3-fold induction of hypothalamic CRH mRNA, pituitary POMC mRNA and RU486-induced ACTH levels were decreased in Lifr -/- mice. High CRH may be caused by increased central TNFalpha and IL-6 expression. Lifr -/- mice demonstrate elevated pituitary glucocorticoid (GR) and mineralocorticoid (MR) receptor mRNA and protein levels, indicating the importance of LIF signaling for HPA axis development.
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, WA 98195-7190, USA.
authors.forename: Carol B
authors.initials: CB
authors.lastname: Ware
authors.forename: Anastasia
authors.initials: A
authors.lastname: Kariagina
authors.forename: Svetlana
authors.initials: S
authors.lastname: Zonis
authors.forename: Dana
authors.initials: D
authors.lastname: Alon
authors.forename: Vera
authors.initials: V
authors.lastname: Chesnokova
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000032:analysis / Q000378:metabolism; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000196:embryology* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D051379:Mice; D008817:Mice, Mutant Strains; D015735:Mifepristone / Q000494:pharmacology; D009154:Mutation; D010903:Pituitary Gland, Anterior / Q000276:immunology; D010913:Pituitary-Adrenal System / Q000196:embryology* / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000032:analysis / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000502:physiology*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D053606:Receptors, OSM-LIF; D015398:Signal Transduction; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507838:Lif protein, mouse; C507841:Lifr protein, mouse; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D018121:Receptors, Cytokine; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D053606:Receptors, OSM-LIF; D014409:Tumor Necrosis Factor-alpha; D015735:Mifepristone; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone