Document Detail


Gonadotropin-releasing hormone (GnRH) agonist leuprolide acetate and GnRH antagonist cetrorelix acetate directly inhibit leiomyoma extracellular matrix production.
MedLine Citation:
PMID:  22901846     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To determine the direct effect that GnRH analogues leuprolide acetate and cetrorelix acetate have on extracellular matrix in human leiomyoma and patient-matched myometrial cells.
DESIGN: Laboratory study.
SETTING: University hospital.
PATIENT(S): None.
INTERVENTION(S): Cell culture, proliferation studies, and messenger RNA and protein analysis.
MAIN OUTCOME MEASURE(S): Expression of GnRHR1, COL1A1, fibronectin, and versican variant V0 in treated leiomyoma cells and patient-matched myometrial cells.
RESULT(S): Leiomyoma cells were treated with GnRH analogues for 6, 24, and 120 hours. Leuprolide treatment for 6 hours resulted in an increase in expression of GnRHR1 (4.02 ± 0.12-fold), COL1A1 (6.41 ± 0.29-fold), fibronectin (9.69 ± 0.18-fold), and versican variant V0 (7.58 ± 0.43-fold). Leiomyoma cells treated with cetrorelix for 6 hours showed a decreased expression of GnRHR1 (0.5 ± 0.15-fold), COL1A1 (3.79 ± 0.7-fold), fibronectin (0.92 ± 0.09-fold), and versican variant V0 (0.14 ± 0.07-fold). Leuprolide treatment of leiomyoma cells at high concentrations (10(-5) M) did not result in an increase in protein production. Cetrorelix treatment of leiomyoma cells for 6 hours showed an increase in fibronectin protein production (3.14 ± 0.09-fold). Protein production of leiomyoma cells treated with cetrorelix for 120 hours demonstrated a decrease in GnRHR1 (0.51 ± 0.07-fold), COL1A1 (0.35 ± 0.07-fold), fibronectin (1.94 ± 0.08-fold), and versican variant V0 (0.77 ± 0.19-fold).
CONCLUSION(S): Our findings demonstrate that GnRH analogue treatment directly regulated COL1A1, fibronectin, and matrix proteoglycan production. The reduction in versican variant V0 gene expression caused by cetrorelix treatment, and its association with the osmotic regulation of leiomyomas, presents a new and innovative approach to therapy for this disease.
Authors:
Joy Lynne Britten; Minnie Malik; Gary Levy; Mirian Mendoza; William H Catherino
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Publication Detail:
Type:  Journal Article; Video-Audio Media     Date:  2012-08-14
Journal Detail:
Title:  Fertility and sterility     Volume:  98     ISSN:  1556-5653     ISO Abbreviation:  Fertil. Steril.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-22     Completed Date:  2013-01-03     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0372772     Medline TA:  Fertil Steril     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1299-307     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Inc.
Affiliation:
Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799, USA.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents, Hormonal / pharmacology*
Cell Proliferation / drug effects
Collagen Type I / biosynthesis
Dose-Response Relationship, Drug
Extracellular Matrix Proteins / biosynthesis*,  genetics
Female
Fibronectins / biosynthesis
Gene Expression Regulation, Neoplastic / drug effects
Gonadotropin-Releasing Hormone / agonists*,  analogs & derivatives*,  antagonists & inhibitors*,  metabolism,  pharmacology
Hormone Antagonists / pharmacology*
Humans
Leiomyoma / genetics,  metabolism*,  pathology
Leuprolide / pharmacology*
RNA, Messenger / metabolism
Receptors, LHRH / drug effects,  genetics,  metabolism
Time Factors
Tumor Cells, Cultured
Uterine Neoplasms / genetics,  metabolism*,  pathology
Versicans / biosynthesis
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Hormonal; 0/Collagen Type I; 0/Extracellular Matrix Proteins; 0/Fibronectins; 0/GNRHR protein, human; 0/Hormone Antagonists; 0/RNA, Messenger; 0/Receptors, LHRH; 0/VCAN protein, human; 0/collagen type I, alpha 1 chain; 126968-45-4/Versicans; 33515-09-2/Gonadotropin-Releasing Hormone; 53714-56-0/Leuprolide; OON1HFZ4BA/cetrorelix

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


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