Effects of Progesterone on iNOS, COX-2, and Collagen Expression in the Cervix

Marx, Stephen; Wentz, Melissa J.; MacKay, Lynette B.; Schlembach, Dietmar; Maul, Holger; Fittkow, Cordula; Given, Randall L.; Vedernikov, Yurij P.; Saade, George R.; Garfield, Robert E.

doi:10.1369/jhc.5a6759.2006

Cited by 43 publications

(37 citation statements)

References 82 publications

(160 reference statements)

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“…Indeed, the experimental findings suggested that the mechanism of progesterone involved an interaction between iNOS and P38MAPK signal pathway [23] . The impact of progesterone on the MAPK activity to suppress NO, which we concerned, were consistent with previous studies [24] .…”

Section: Discussionsupporting

confidence: 92%

The nongenomic effects of progesterone in repressing iNOS activation through P38MAPK pathways in gonococci-infected polymorphonuclear leukocytes and the clinical significance

Chen

Lin

et al. 2010

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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Progesterone has nongenomic effects on inducible nitric oxide synthase (iNOS), which is mediated by mitogen activated protein kinase (MAPK) pathways. This effect is supposed to have some potential association with asymptomatic gonococcal infections in women by immunological depression. In this study, polymorphonuclear leukocytes (PMNs) challenged by gonococci were used to study the nongenomic effects of progesterone. The activation of iNOS was assessed by measuring [(3)H] L-arginine converses to [(3)H] L-citrulline, and the activity of MAPK was detected by Western blot. It was found that the activity of iNOS and the yields of NO were enhanced significantly in gonococci-challenged PMNs compared with the controls (P<0.01). Progesterone could repress the activation of iNOS through P38MAPK pathway within PMNs (P<0.05), which could be blocked by SB203580 (P<0.01), but not by actinomycin D (P>0.05). It was also found subsequently that in the serum specimens collected from gonococci-infected but asymptomatic women, the progesterone level was higher than that in women with severe symptoms (P<0.01). Moreover, the yield of NO had an inverse correlation with progesterone. With these results it suggested that the rapid nongenomic effects of progesterone may inhibit iNOS activation and NO yields mediated by P38MAPK pathways, which were supposed to be concerned with asymptomatic women infected with gonococci.

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Section: Discussionsupporting

confidence: 92%

The nongenomic effects of progesterone in repressing iNOS activation through P38MAPK pathways in gonococci-infected polymorphonuclear leukocytes and the clinical significance

Chen

Lin

et al. 2010

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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“…COX-2, resulting in transcriptional activation that promote uterine contractility, is important during gestation and parturition (6,7,22,23). The COX-2 mRNA levels in our study appeared to be compatible with the several studies reported in literature (3,7,31,15,28). According to our results, COX-2 mRNA levels gradually increase at the beginning of pregnancy from day 10 to 20 and expression of COX-2 was at a maximum on day 21 (parturition).…”

Section: Discussionsupporting

confidence: 92%

“…Studies show that iNOS and COX-2 enzymes were co-localized during gestation under normal conditions (25,30). Marx et al also demonstrated the relationship between COX-2 and iNOS in the control of cervical ripening and parturition under both term and preterm laboring conditions (15). Moreover, recent studies reported that iNOS mRNA levels had a tendency to decrease whereas COX-2 mRNA levels increased as pregnancy progressed to term, demonstrating an inverse relationship (7,8,24).…”

Section: Discussionmentioning

confidence: 94%

“…Several studies have also demonstrated a dramatic increase in the inducible form of COX (COX-2) expression at both mRNA and protein levels in both preterm and term labor (3,7,31). Increased COX-2 mRNA expression that occurs under term and preterm laboring conditions was shown by Marx et al (15). In addition, Arslan and Zingg showed that COX-2 mRNA levels were increased in the uterus from the seventh day of rat pregnancy until parturition (3).…”

Section: Discussionmentioning

confidence: 99%

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The changes of Inducible Nitric Oxide Synthase, Endothelial Nitric Oxide Synthase and Cyclooxygenase-2 mRNA expressions in intrauterine tissues of pregnant rats

YAR¹

2012

Ankara Üniversitesi Veteriner Fakültesi Dergisi

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Summary: Prostaglandins (PGs) are produced by the intrauterine tissues of pregnancy and play important role in all of the physiological processes of parturition. PGs are synthesized from arachidonic acid by the action of cyclooxygenase (COX). Nitric oxide (NO) is a potent smooth muscle relaxant and is considered to be an important local mediator that suppresses uterine contractility. There may be an interaction between the NO and PG pathways in regulating the nitric oxide synthase (NOS) and COX expression and this interaction may play a critical role in the control of cervical ripening and parturition. The purpose of this study is to examine the expression of cyclooxygenase-2 (COX-2), inducible NOS (iNOS) and endothelial NOS (eNOS) mRNA levels during gestation, parturition, and postpartum in pregnant rat uterus. Forty-two pregnant Sprague Dawley rats were randomly divided into 7 groups. Both uterine horns were removed and the pups and placentas were discarded. Complementary DNA (cDNA) was synthesized after isolation of total RNA from the tissues. The relative expression of iNOS, eNOS and COX-2 genes were measured by quantitative real-time polymerase chain reaction (QRT-PCR). The mRNA level of iNOS was increased during gestation; highest level in parturition and then it decreased at postpartum. The eNOS mRNA level was generally low during gestation in all groups and was significantly increased at postpartum. The COX-2 mRNA levels decreased as the pregnancy progressed to term with the highest level occurring on day 21 and the lovest levels during the postpartum period. In conclusion, there may be an interaction between the NO and PG pathways in cervical ripening and parturition. These results may show that mRNA levels of eNOS, iNOS and COX-2 genes may be effective cervical ripening during pregnancy and parturition.Key words: cyclooxygenase-2, gestation, intrauterine tissue, nitric oxide synthase, parturition. Gebe ratların rahim içi dokularında Uyarılabilir Nitrik Oksit Sentaz, Endotelyal Nitrik Oksit Sentaz ve Siklooksijenaz-2 mRNA ekspresyon değişiklikleriÖzet: Prostaglandinler (PG) gebelikte rahim içi dokularda üretilirler ve doğum sırasındaki tüm fizyolojik süreçlerde önemli rol oynarlar. PG'ler araşidonik asitten siklooksijenaz (COX) enziminin aktivitesi ile sentezlenirler. Nitrik oksit (NO) güçlü bir düz kas gevşetici ve uterus kasılmasını baskılayan önemli bir bölgesel ara bulucu olarak kabul edilir. Nitrik oksit sentaz (NOS) ve COX ifadelenmesinin düzenlenmesinde NO ve PG yolakları arasında bir etkileşim olabilir ve bu etkileşim servikal olgunlaşma ve doğumun kontrolünde kritik bir rol oynayabilir. Bu çalışmanın amacı, hamile rat uterusunda gebelikte, doğum sırasında ve doğum sonrasında siklooksijenaz-2 (COX-2), uyarılabilir NOS (iNOS) ve endotelyal NOS (eNOS) mRNA düzeylerini incelemektir. Kırk iki hamile Sprague Dawley rat rastgele olarak 7 gruba ayrıldı. Her iki uterin boynuzu ve yavrular ve plasenta çıkarıldı. Tamamlayıcı DNA (cDNA) dokulardan total RNA izole edildikten sonra sentezlendi. iNOS, eNOS v...

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“…MMP-2 and MMP-9 in the cervical ripening process has been indicated in cervical ripening. 6,7 To summarize, the complex interactions of various cytokines bring about profound changes in the proteoglycans in the cervix which eventually leads to cervical ripening.…”

Section: Introductionmentioning

confidence: 99%