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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adrenocorticotropic Hormone / analysis
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Adrenocorticotropic Hormone / metabolism
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Animals
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Corticotropin-Releasing Hormone / genetics
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Corticotropin-Releasing Hormone / metabolism
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Hypothalamo-Hypophyseal System / embryology*
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Hypothalamo-Hypophyseal System / metabolism
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Interleukin-6 / metabolism
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Leukemia Inhibitory Factor
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Leukemia Inhibitory Factor Receptor alpha Subunit
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Mice
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Mice, Mutant Strains
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Mifepristone / pharmacology
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Mutation
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Pituitary Gland, Anterior / immunology
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Pituitary-Adrenal System / embryology*
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Pituitary-Adrenal System / metabolism
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Pro-Opiomelanocortin / genetics
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RNA, Messenger / analysis
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RNA, Messenger / metabolism
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Receptors, Corticotropin-Releasing Hormone / analysis
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Receptors, Corticotropin-Releasing Hormone / metabolism
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Receptors, Cytokine / genetics
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Receptors, Cytokine / physiology*
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Receptors, Glucocorticoid / metabolism
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Receptors, Mineralocorticoid / metabolism
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Receptors, OSM-LIF
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Signal Transduction*
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Transcription, Genetic
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Tumor Necrosis Factor-alpha / metabolism
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Up-Regulation
Substances
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Interleukin-6
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Leukemia Inhibitory Factor
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Leukemia Inhibitory Factor Receptor alpha Subunit
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Lif protein, mouse
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Lifr protein, mouse
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RNA, Messenger
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Receptors, Corticotropin-Releasing Hormone
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Receptors, Cytokine
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Receptors, Glucocorticoid
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Receptors, Mineralocorticoid
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Receptors, OSM-LIF
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Tumor Necrosis Factor-alpha
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Mifepristone
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Pro-Opiomelanocortin
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Adrenocorticotropic Hormone
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Corticotropin-Releasing Hormone