AJP - Endo AJP: Renal Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Endocrinol Metab 289: E857-E863, 2005. First published June 28, 2005; doi:10.1152/ajpendo.00577.2004
0193-1849/05 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
289/5/E857    most recent
00577.2004v2
00577.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (3)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kariagina, A.
Right arrow Articles by Chesnokova, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kariagina, A.
Right arrow Articles by Chesnokova, V.

Leukemia inhibitory factor regulates glucocorticoid receptor expression in the hypothalamic-pituitary-adrenal axis

Anastasia Kariagina, Svetlana Zonis, Mahta Afkhami, Dmitry Romanenko, and Vera Chesnokova

Cedars-Sinai Medical Center and David Geffen School of Medicine at University of California, Los Angeles, California

Submitted 7 December 2004 ; accepted in final form 20 June 2005

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine belonging to the gp130 family. LIF is induced peripherally and within the brain during inflammatory or chronic autoimmune diseases and is a potent stimulator of the hypothalamic-pituitary-adrenal (HPA) axis. Here we investigated the role of LIF in mediating glucocorticoid receptor (GR) expression in the HPA axis. LIF treatment (3 µg/mouse, ip) markedly decreased GR mRNA levels in murine hypothalamus (5-fold, P < 0.01) and pituitary (1.7-fold, P < 0.01) and downregulated GR protein levels. LIF decreased GR expression in murine corticotroph cell line AtT20 within 2 h, and this effect was sustained for 8 h after treatment. LIF-induced GR mRNA reduction was abrogated in AtT20 cells overexpressing dominant-negative mutants of STAT3, indicating that intact JAK-STAT signaling is required to mediate LIF effects on GR expression. Conversely, mice with LIF deficiency exhibited increased GR mRNA levels in the hypothalamus and pituitary (3.5- and 3.5-fold, respectively; P < 0.01 for both) and increased GR protein expression when compared with wild-type littermates. The suppressive effects of dexamethasone on GR were more pronounced in LIF-null animals. These data suggest that LIF maintains the HPA axis activation by decreasing GR expression and raise the possibility that LIF might contribute to the development of central glucocorticoid resistance during inflammation.

LIF-null mice; AtT20 cells


Address for reprint requests and other correspondence: V. Chesnokova, Dept. of Medicine, Div. of Endocrinology, Davis Bldg., Rm. 3019, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048 (e-mail: chesnokovav{at}cshs.org)




This article has been cited by other articles:


Home page
 Exp PhysiolHome page
J. Gerez, J. Bonfiglio, S. Sosa, D. Giacomini, M. Acuna, A. Carbia Nagashima, M. J. Perone, S. Silberstein, U. Renner, G. K. Stalla, et al.
Molecular transduction mechanisms of cytokine-hormone interactions: role of gp130 cytokines
Exp Physiol, September 1, 2007; 92(5): 801 - 806.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2005 by the American Physiological Society.