Document Detail


Treatment with an inhibitor of catechol-O-methyltransferase activity reduces preterm birth and impedes cervical resistance to stretch in pregnant rats.
MedLine Citation:
PMID:  18042640     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Catechol-O-methyltransferase (COMT) enzyme catalyzes the methylation of the 2- or 4-hydroxyestrogens to 2- or 4-methoxyestrogens. Both the hydroxyestrogens and methoxyestrogens have been shown to block or enhance the effects of estrogen respectively. Our objective was to investigate the potential role of COMT in parturition and cervical ripening using a rat model. Immunohistochemistry was conducted to detect and localize the COMT protein in rat uterine tissues during pregnancy. We measured the longitudinal changes in urinary 2-hydroxyestrogen before, during, and after pregnancy in rats. Animal studies were conducted to determine the effect of treatment with a selective COMT inhibitor on (1) mifepristone-induced preterm birth and (2) cervical resistance to stretch in pregnant rats. The intensity of staining for the COMT protein differed within the luminal epithelium, uterine gland epithelium, endometrium, and myometrium during pregnancy. Levels of staining for the COMT protein in rat myometrium were highest on day 1 and lowest on days 8 and 13, but high levels returned by days 16 and 19 of pregnancy. The levels of urinary 2-hydroxyestrogen gradually increased in the first 2 weeks of pregnancy, peaked from days 16 to 18 of pregnancy, and then gradually returned to pre-pregnancy levels after delivery. The percentage of pups retained in the uterus of pregnant rats treated with both mifepristone and COMT inhibitor (48 +/- 15%) was significantly higher (P < 0.05) when compared with the value of pregnant rats treated with mifepristone alone (12 +/- 4%). The resistance to stretch was significantly higher (P < 0.05) in cervical tissues from the pregnant rats treated with COMT inhibitor (0.28) when compared with cervical tissues taken from rats treated with vehicle control (0.18). Modulation of COMT activity may play a role in the regulation of myometrial contractility and cervical ripening during pregnancy.
Authors:
Melissa J Wentz; Shao-Qing Shi; Leili Shi; Salama A Salama; Hassan M Harirah; Hala Fouad; Robert E Garfield; Ayman Al-Hendy
Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Reproduction (Cambridge, England)     Volume:  134     ISSN:  1470-1626     ISO Abbreviation:  Reproduction     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-11-28     Completed Date:  2008-04-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100966036     Medline TA:  Reproduction     Country:  England    
Other Details:
Languages:  eng     Pagination:  831-9     Citation Subset:  IM    
Affiliation:
Department of Obstetrics and Gynecology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555-0587, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Benzophenones / pharmacology*
Biological Markers / urine
Catechol O-Methyltransferase / analysis,  antagonists & inhibitors*
Cervical Ripening / drug effects
Cervix Uteri / chemistry,  drug effects,  enzymology*
Estradiol / analogs & derivatives,  urine
Estriol / analogs & derivatives,  urine
Female
Hydroxyestrones / urine
Immunohistochemistry
Mifepristone
Models, Animal
Obstetric Labor, Premature / enzymology,  prevention & control*
Pregnancy
Rats
Rats, Sprague-Dawley
Chemical
Reg. No./Substance:
0/Benzophenones; 0/Biological Markers; 0/Hydroxyestrones; 1232-80-0/2-hydroxyestriol; 125628-97-9/Ro 41-0960; 362-05-0/2-hydroxyestradiol; 362-06-1/2-hydroxyestrone; 50-27-1/Estriol; 50-28-2/Estradiol; 84371-65-3/Mifepristone; EC 2.1.1.6/Catechol O-Methyltransferase

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


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