Document Detail


Leukemia inhibitory factor (LIF) modulates pro-opiomelanocortin (POMC) gene regulation in stably transfected AtT-20 cells overexpressing LIF.
MedLine Citation:
PMID:  9657069     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Leukemia inhibitory factor (LIF) levels are elevated in sepsis and correlate with shock and poor prognosis. We have previously shown that lipopolysaccharide (LPS) administration induces hypothalamic and pituitary LIF expression in vivo, which is associated with the acute rise in circulating adrenocorticotrophic hormone (ACTH) levels. As AtT-20 cells respond to LIF, we established murine LIF (mLIF) stably transfected AtT-20 cell lines to study LIF regulation of pro-opiomelanocortin (POMC) expression and ACTH secretion. Our results show that mLIF transfectants accumulated mLIF (up to 15.6 +/- 3.2 ng/mL after 24 h) as well as increased ACTH secretion (up to 2.4-fold above control cells) in conditioned medium. The magnitude of ACTH induction correlated with mLIF concentrations in different transfectants (r = 0.75-0.88, p < 0.05). Moreover, mLIF transfectants showed a higher sensitivity to CRH stimulation with an increased ACTH production within 8 h (p < 0.05), whereas control cells were responsive to CRH at 24 h. Additionally, mLIF transfectants exhibited a maximum threefold ACTH induction, compared to 1.7-fold in control cells. Furthermore, mLIF transfectants have a blunted dexamethasone-mediated inhibition of ACTH (35% inhibition in control cells vs no inhibition in mLIF-transfected cells at 24 h). These findings support and extend the previous observations of LIF acting at the pituitary level, and indicate that mLIF stably-transfected AtT-20 cells are a useful model for studying mLIF-mediated gene regulation in pituicytes.
Authors:
Q L Li; H Yano; S G Ren; X Li; T C Friedman; S Melmed
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Endocrine     Volume:  7     ISSN:  1355-008X     ISO Abbreviation:  Endocrine     Publication Date:  1997 Dec 
Date Detail:
Created Date:  1998-10-02     Completed Date:  1998-10-02     Revised Date:  2010-06-24    
Medline Journal Info:
Nlm Unique ID:  9434444     Medline TA:  Endocrine     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  325-30     Citation Subset:  IM    
Affiliation:
Department of Medicine, Cedars-Sinai Research Institute-UCLA School of Medicine, USA.
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MeSH Terms
Descriptor/Qualifier:
Adrenocorticotropic Hormone / metabolism
Blotting, Northern
Cell Line
Corticotropin-Releasing Hormone / blood
Gene Expression Regulation / drug effects*
Growth Inhibitors / biosynthesis*,  genetics,  physiology*
Humans
Interleukin-6*
Leukemia Inhibitory Factor
Lymphokines / biosynthesis*,  genetics,  physiology*
Pro-Opiomelanocortin / biosynthesis*,  genetics
RNA, Messenger / biosynthesis
Radioimmunoassay
Transfection
Grant Support
ID/Acronym/Agency:
DA-00276/DA/NIDA NIH HHS; DK-287235/DK/NIDDK NIH HHS; DK-50238/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Growth Inhibitors; 0/Interleukin-6; 0/LIF protein, human; 0/Leukemia Inhibitory Factor; 0/Lymphokines; 0/RNA, Messenger; 66796-54-1/Pro-Opiomelanocortin; 9002-60-2/Adrenocorticotropic Hormone; 9015-71-8/Corticotropin-Releasing Hormone

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