Up-regulation of nitric oxide synthase and modulation of the guanylate cyclase activity by corticotropin-releasing hormone but not urocortin II or urocortin III in cultured human pregnant myometrial cells

Aggelidou, Eleni; Hillhouse, Edward W.; Grammatopoulos, Dimitris K.

doi:10.1073/pnas.052296399

Cited by 74 publications

(54 citation statements)

References 57 publications

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“…[22][23][24][25][26][27][28] Higher NO values found in late preterm mothers compared with term mothers Table 2 complement those reports. [22][23][24][25][26][27][28] Some earlier studies reported a greater expression of the isoforms of NOS (eNOS, iNOS) in the myometrium of the preterm 'not in labour' group compared with all other groups: non-pregnant women, pregnant women in the early third trimester, and pregnant women at term (both before and after labour). 27,28 Since iNOS promotes inflammation, and inflammation in turn promotes pro-oxidant formation, this may explain why late preterm mothers and not term mothers had more elevated plasma NO concentrations and reduced erythrocyte antioxidant (GPx) activity Table 2. 12 High prooxidant levels, coupled with reduced antioxidants, signify a disturbance of the pro-oxidant-antioxidant balance otherwise known as oxidative stress.…”

Section: Discussionsupporting

confidence: 62%

“…29,30 The placenta synthesises, on a weight-for-weight basis, more NO than the foetal membrane or the myometrium. 26 From early pregnancy, the mitochondria replete placenta influences maternal homeostasis and consumes about 1% of the basal metabolic rate of the pregnant woman. 31 The placenta in addition, is highly vascular and, on exposure to high maternal oxygen tension, generates superoxide ( Tables 1 and 2].…”

Section: Discussionmentioning

confidence: 99%

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Nitric Oxide and Antioxidant Enzymes in Venous and Cord Blood of Late Preterm and Term Omani Mothers

Abiaka¹,

Machado²

2012

SQUMJ

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This study assessed the role of oxidative stress in parturition in Omani mothers following growing reports that late preterm neonates were at greater risk than term neonates of perinatal death. Methods: Venous blood samples were collected during labour, and cord (neonatal) blood samples were taken after childbirth in late preterm and term from women at Sultan Qaboos University Hospital, Oman. Plasma nitric oxide (NO) concentrations, erythrocyte catalase (CAT). Erythrocyte glutathione peroxidase (GPx) activities were measured using spectrophotometric methods. Results: When compared with term mothers, late preterm mothers had markedly higher NO concentrations (µmol/L) 17.1 ± 3.3 versus 11.0 ± 5.5 (P <0.0001), and lower GPx values (U/g Hb) 94.1 ± 12.9 versus 110.4 ± 12.3 (P <0.0001). Late preterm mothers were significantly younger (P = 0.027) than term mothers and had neonates that weighed significantly less (P <0.0001) than term neonates. GPx activity was significantly reduced (P = 0.001) in late preterm neonates as compared to term neonates. CAT showed no change in activity in any comparison. Conclusion: Distinctly higher values of NO and lower GPx activity were found in late preterm mothers relative to term mothers; also, lower GPx in late preterm neonates relative to term neonates suggested a pro-oxidant-antioxidant imbalance due to the greater oxidative burden in late preterm parturition.

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Nitric Oxide and Antioxidant Enzymes in Venous and Cord Blood of Late Preterm and Term Omani Mothers

Abiaka¹,

Machado²

2012

SQUMJ

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“…In mixed cultures, CRH receptor expression was barely detectable in stromal cells in vitro (data not shown). This might be due to tissue manipulation upon preparation of primary cell cultures, since studies on human myometrial cells have shown loss of CRH receptors as the number of passages of primary cultures increases (Linton et al 2001, Aggelidou et al 2002.…”

Section: Fishmentioning

confidence: 99%

Expression and signalling characteristics of the corticotrophin-releasing hormone receptors during the implantation phase in the human endometrium

Karteris

Papadopoulou²,

Grammatopoulos³

et al. 2004

Journal of Molecular Endocrinology

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Corticotrophin-releasing hormone (CRH) has been identified in several peripheral tissues, including the female reproductive organs. CRH is expressed in the placenta, myometrium, epithelial endometrium and the endometrial stromal cells at all phases of the menstrual cycle. Similarly, CRH receptors are present in pregnant and non-pregnant myometrium, placenta and endometrium. Putative roles of CRH in the endometrium include involvement in implantation, decidualisation and maintenance of pregnancy. In this study we sought to investigate in detail the CRH receptor repertoire expressed in the human endometrium and their signalling characteristics. Using RT-PCR we were able to demonstrate the expression of CRH receptor 1 (CRH-R1 ) and CRH-R2 in the human endometrium. CRH-R1 was present in 40% of endometrial cDNAs examined. No apparent expression of CRH-R2 , CRH-R2 or any other CRH-R1 splice variants was detected. Chemical cross-linking studies with 125 I-ovine CRH revealed that the endometrial CRH receptor has a molecular weight of 45 kDa. Using the non-hydrolysable photoreactive analogue [ -32 P]GTP-azidoanilide and peptide antisera raised against G-protein -subunits, we then studied coupling of endometrial CRH receptors to G proteins. Treatment of endometrial membranes with human CRH (100 nM) increased the labelling of Gq and Gs, but not Gi or Go. These results were supported by experiments in epithelial cells of the non-pregnant human endometrium in the secretory phase which showed that CRH induced increases in both cAMP and inositol trisphosphate levels. These results suggested that CRH may exert multiple effects in the human endometrium via distinct signalling cascades. These events are possibly mediated via different receptor subtypes.

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“…9, No. 1,2003 reduced the number of escape failures and ACTH administration (100 mg/rat, i.p.) blocked this effect.…”

Section: Elevated Plus Maze (Epm)mentioning

confidence: 99%

The Pharmacology of CP‐154,526, a Non‐Peptide Antagonist of the CRH1 Receptor: A Review

2003

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Since CRH has been shown to mediate stress-induced physiological and behavioral changes, it has been hypothesized that CRH receptor antagonists may have therapeutic potential in disorders that involve excessive CRH activity. CP-154,526 and its close analog antalarmin are potent, brain-penetrable, selective nonpeptide CRH1 receptor antagonists that were discovered in an effort to develop compounds with efficacy in CNS disorders precipitated by stress. Since its discovery many investigators have used CP-154,526 as a tool to study the pharmacology of CRH and its receptors and to evaluate its therapeutic potential in a variety of CNS and peripheral disorders. Systemically-administered CP-154,526 has been demonstrated to antagonize CRH-and stress-induced neuroendocrine, neurochemical, electrophysiological, and behavioral effects.These findings support the hypothesis that CRH1 receptor antagonists may have therapeutic utility in a number of neuropsychiatric disorders. CP-154,526, as well as other CRH1 receptor antagonists that have since been discovered, have also shown activity in several preclinical models of anxiety, depression, and substance abuse, while having little effect on locomotor activity and motor function. Although these effects are on occasion inconsistent among different laboratories, clinical evaluation of CRH1 antagonists appears justified on the basis of these and clinical data implicating the involvement of CRH in several CNS disorders. The effects of CRH1 antagonists on cognition, neurodegeneration, inflammation, and the gastrointestinal system have not been as extensively characterized and additional studies will be necessary to evaluate their therapeutic potential in these areas.

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Up-regulation of nitric oxide synthase and modulation of the guanylate cyclase activity by corticotropin-releasing hormone but not urocortin II or urocortin III in cultured human pregnant myometrial cells

Cited by 74 publications

References 57 publications

Nitric Oxide and Antioxidant Enzymes in Venous and Cord Blood of Late Preterm and Term Omani Mothers

Nitric Oxide and Antioxidant Enzymes in Venous and Cord Blood of Late Preterm and Term Omani Mothers

Expression and signalling characteristics of the corticotrophin-releasing hormone receptors during the implantation phase in the human endometrium

The Pharmacology of CP‐154,526, a Non‐Peptide Antagonist of the CRH1 Receptor: A Review

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