Document Detail

Gonadotropin releasing hormone and transforming growth factor beta activate mitogen-activated protein kinase/extracellularly regulated kinase and differentially regulate fibronectin, type I collagen, and plasminogen activator inhibitor-1 expression in leiomyoma and myometrial smooth muscle cells.
MedLine Citation:
PMID:  15531510     Owner:  NLM     Status:  MEDLINE    
GnRH analog (GnRHa) and TGF-beta act directly on leiomyoma/myometrial smooth muscle cells (LSMCs and MSMCs) regulating diverse activities resulting in leiomyoma growth and regression. Because GnRH and TGF-beta receptor signaling is in part mediated through the MAPK pathway, we determined whether the contribution of MAPK/ERK and transcriptional activation of c-fos and c-jun, result in differential regulation of type I collagen, fibronectin, and plasminogen activator inhibitor 1 (PAI-1) gene expression, whose products are known to influence extracellular matrix turnover, which is critical in leiomyoma growth and GnRHa-induced regression. We found that GnRHa and TGF-beta in a dose- and time-dependent manner increased the level of phosphorylated ERK1/2 (pERK1/2) in LSMCs and MSMCs. GnRHa and TGF-beta increased ERK1/2 nuclear accumulation resulting in differential regulation of c-fos and c-jun mRNA expression via downstream signaling from MAPK kinase (MEK)1/2, because pretreatment with U0126, a synthetic inhibitor of MEK1/2, abolished basal and GnRHa- and TGF-beta-induced pERK1/2 and the expression of c-fos and c-jun. LSMCs and MSMCs also express fibronectin, type I collagen, and PAI-1 mRNA, and GnRHa and TGF-beta altered their expression in a cell-specific manner through MEK1/2. We concluded that GnRHa and TGF-beta acting through a MAPK/ERK pathway and transcriptional activation of c-fos/c-jun results in differential regulation of specific genes whose products may in part influence the outcome of leiomyoma growth and regression.
Li Ding; Jingxia Xu; Xiaoping Luo; Nasser Chegini
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  89     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-11-08     Completed Date:  2004-12-02     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5549-57     Citation Subset:  AIM; IM    
Department of Obstetrics and Gynecology, University of Florida, Box 100294, Gainesville, Florida 32610, USA.
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MeSH Terms
Collagen Type I / genetics*
Enzyme Activation
Fibronectins / genetics*
Gene Expression Regulation / drug effects*
Genes, fos
Genes, jun
Gonadotropin-Releasing Hormone / analogs & derivatives*,  pharmacology*
Leiomyoma / metabolism*
Mitogen-Activated Protein Kinases / metabolism*
Myocytes, Smooth Muscle / metabolism*
Myometrium / metabolism*
Plasminogen Activator Inhibitor 1 / genetics*
Transforming Growth Factor beta / pharmacology*
Uterine Neoplasms / metabolism*
Grant Support
Reg. No./Substance:
0/Collagen Type I; 0/Fibronectins; 0/Plasminogen Activator Inhibitor 1; 0/Transforming Growth Factor beta; 33515-09-2/Gonadotropin-Releasing Hormone; 79561-22-1/LHRH, Ala(6)-Gly(10)-ethylamide-; EC Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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