Opposing effects of pituitary leukemia inhibitory factor and SOCS-3 on the ACTH axis response to inflammation

Cedars-Sinai Research Institute-University of California Los Angeles School of Medicine, Los Angeles, California 90048 We have shown that leukemia inhibitory factor (LIF) and suppressor of cytokine signaling (SOCS)-3 are expressed in the hypothalamus and pituitary and that LIF induces proopiomelanoc...

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Bibliographic Details
Published in:American journal of physiology: endocrinology and metabolism 2002-05, Vol.282 (5), p.E1110-E1118
Main Authors: Chesnokova, Vera, Kariagina, Anastasia, Melmed, Shlomo
Format: Article
Language:English
Subjects:
Acute Disease
Adrenocorticotropic Hormone - blood
Animals
Corticosterone - blood
Cytokines - genetics
Female
Gene Expression - immunology
Growth Inhibitors - genetics
Growth Inhibitors - metabolism
Hypothalamo-Hypophyseal System - immunology
Hypothalamo-Hypophyseal System - metabolism
Inflammation - chemically induced
Inflammation - immunology
Inflammation - metabolism
Interleukin-6
Leukemia Inhibitory Factor
Lipopolysaccharides
Lymphokines - genetics
Lymphokines - metabolism
Male
Mice
Mice, Knockout
Neuroimmunomodulation - physiology
Pituitary-Adrenal System - immunology
Pituitary-Adrenal System - metabolism
Pro-Opiomelanocortin - genetics
Proteins - genetics
Proteins - metabolism
Repressor Proteins
RNA, Messenger - analysis
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins
Transcription Factors
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Summary:Cedars-Sinai Research Institute-University of California Los Angeles School of Medicine, Los Angeles, California 90048 We have shown that leukemia inhibitory factor (LIF) and suppressor of cytokine signaling (SOCS)-3 are expressed in the hypothalamus and pituitary and that LIF induces proopiomelanocortin (POMC) and ACTH, whereas SOCS-3 abrogates corticotroph POMC gene transcription and ACTH secretion. Here, we determined the role of pituitary LIF and SOCS-3 in regulating hypothalamo-pituitary-adrenal (HPA) axis inflammatory responses. Murine pituitary LIF expression was induced up to eightfold after intraperitoneal injection of lipopolysaccharide or tumor necrosis factor- , concordant with elevated plasma levels of ACTH and corticosterone. In LIF knockout (LIFKO) mice, induction of both ACTH and corticosterone were attenuated. LIF deletion was associated with elevated ( P  
ISSN:0193-1849
1522-1555
DOI:10.1152/ajpendo.00442.2001