help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
This version published online on October 29, 2009
Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2009-0595
This Article
Right arrow Author Manuscript (PDF)
Right arrow Supplemental Data
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Google Scholar
Right arrow Articles by Lekva, T.
Right arrow Articles by Jemtland, R.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lekva, T.
Right arrow Articles by Jemtland, R.

Submitted on March 18, 2009
Accepted on September 29, 2009

The Glucocorticoid-Induced Leucine Zipper Gene (GILZ) Expression Decreases after Successful Treatment of Patients with Endogenous Cushing's Syndrome and May Play a Role in Glucocorticoid-Induced Osteoporosis

Tove Lekva, Jens Bollerslev*, Cybéle Kristo, Ole Krisoffer Olstad, Thor Ueland, and Rune Jemtland

Section of Endocrinology, Department of Medicine (T.L., J.B., T.U., R.J.), Research Institute for Internal Medicine (T.L., T.U.), Section of Rheumatology (C.K.), Oslo University Hospital, Rikshospitalet, N-0027 Oslo, Norway; and Department of Clinical Chemistry (O.K.O.), Oslo University Hospital, Ulleval, University of Oslo, N-0407 Oslo, Norway

* To whom correspondence should be addressed. E-mail: jens.bollerslev{at}medisin.uio.no.

Context: Glucocorticoid-induced bone loss is a serious complication in patients with endogenous Cushing's syndrome. However, the mechanism(s) by which excess glucocorticoids influence bone metabolism is not completely understood.

Objective: The aim of the study was to investigate the functional role of glucocorticoid-induced leucine zipper (GILZ) in bone remodeling with special focus on glucocorticoid-induced osteoporosis (GIO).

Patients: Nine patients with endogenous Cushing's syndrome participated in the study.

Research Design and Methods: We analyzed bone biopsies from Cushing's patients before and after treatment to screen for expressional candidate genes with putative roles in GIO. Microarray analysis combined with real-time RT-PCR revealed that the gene encoding GILZ ranked among the topmost regulated genes and was selected for functional characterization in vitro.

Results: GILZ mRNA was expressed by human fetal osteoblasts (hFOB), human mesenchymal stem cells (hMSC), osteoblasts differentiated from hMSC, and osteoclasts. GILZ was increased by dexamethasone in a time- and dose-dependent manner in hFOB. Inhibition of GILZ in hFOB cells by small interfering RNA decreased typical osteoblast-related genes, suggesting a physiological role in promoting osteoblast maturation. Our data further support a functional role for GILZ in normal bone remodeling by modulating expression of TNF-(ligand) receptor superfamily/osteoprotegerin in favor of increased ratio in hFOB. Finally, osteoclasts exposed to conditioned media from GILZ-silenced hFOB indicated effects on osteoclast activity.

Conclusion: Taken together, these results implicate the transcription factor GILZ in the pathophysiology of GIO by regulating osteoblast maturation and bone turnover.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2009 by The Endocrine Society