Gene regulation of neurokinin B and its receptor NK3 in late pregnancy and pre-eclampsia

School of Life Sciences, Kingston University London, Penrhyn Road, Kingston-upon-Thames, Surrey, UK.
Molecular Human Reproduction (Impact Factor: 3.75). 08/2006; 12(7):427-33. DOI: 10.1093/molehr/gal025
Source: PubMed

ABSTRACT Elevated circulating levels of the tachykinin, neurokinin B (NKB), have been observed in women with pre-eclampsia during the third trimester of pregnancy. Currently, the molecular mechanisms responsible for these increased levels remain unknown. To understand the molecular regulation, we have compared the differences in gene expression of the tachykinins and their receptors in control and pre-eclamptic placentae and the responses of the TAC3 gene encoding NKB to proposed physiological triggers of pre-eclampsia including hypoxia and oxidative stress using real-time quantitative PCR. We have determined the placenta to be the main site of TAC3 expression with levels 2.6-fold higher than the brain. TAC3 expression was found to be significantly higher in pre-eclamptic placenta (1.7-fold, P < 0.05) than in normal controls. No evidence was found that hypoxia and oxidative stress were responsible for increases in TAC3 expression. In rat placenta, a longitudinal study in normal late pregnancy was associated with a significant down-regulation of the NKB/NK3 ligand-receptor pair (P < 0.05). The present data suggest that the increased placental expression of TAC3 is part of the mechanism leading to the increased circulating levels of NKB in pre-eclampsia.

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Available from: Nigel M Page, Feb 19, 2014
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    • "The particular ligand/receptor system NKB/NK3R, (encoded by TAC3/TACR3), previously investigated only for preeclampsia, alcohol, and cocaine dependence [73–75], gained an increasingly important role in human reproductive axis and in CHH onset in the last seven years. So far, over 40 CHH patients with TAC3 and TACR3 mutations have been reported, with a worldwide distribution [45, 76–79]. "
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    ABSTRACT: Central hypogonadotropic hypogonadism (CHH) is an emerging pathological condition frequently associated with overweight, metabolic syndrome, diabetes, and midline defects. The genetic mechanisms involve mutations in at least twenty-four genes regulating GnRH neuronal migration, secretion, and activity. So far, the mechanisms underlying CHH, both in prepubertal and in adulthood onset forms, remain unknown in most of the cases. Indeed, all detected gene variants may explain a small proportion of the affected patients (43%), indicating that other genes or epigenetic mechanisms are involved in the onset of CHH. The aim of this review is to summarize the current knowledge on genetic background of CHH, organizing the large amount of data present in the literature in a clear and concise manner, to produce a useful guide available for researchers and clinicians.
    International Journal of Endocrinology 09/2014; 2014:649154. DOI:10.1155/2014/649154 · 1.95 Impact Factor
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    • "Satake). logical effects regulated by TKs in reproductive tracts including sperm motility induced by SP [28], uterine contractions stimulated by SP, NKA, and NKB [20–22,24], the elevation of circulating NKB in pre-eclampsia or pregnancy via enhanced expression of the TAC3 gene in the placenta [14] [18], and the stimulation of gonadotropinreleasing hormone release by NKB in concert with kisspeptin in the hypothalamus [27] [36]. These findings suggest the multifunctionality of TKs in genital organs. "
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    ABSTRACT: We previously substantiated that Ci-TK, a tachykinin of the protochordate, Ciona intestinalis (Ci), triggered oocyte growth from the vitellogenic stage (stage II) to the post-vitellogenic stage (stage III) via up-regulation of the gene expression and enzymatic activity of the proteases: cathepsin D, carboxypeptidase B1, and chymotrypsin. In the present study, we have elucidated the localization, gene expression and activation profile of these proteases. In situ hybridization showed that the Ci-cathepsin D mRNA was present exclusively in test cells of the stage II oocytes, whereas the Ci-carboxypeptidase B1 and Ci-chymotrypsin mRNAs were detected in follicular cells of the stage II and stage III oocytes. Double-immunostaining demonstrated that the immunoreactivity of Ci-cathepsin D was largely colocalized with that of the receptor of Ci-TK, Ci-TK-R, in test cells of the stage II oocytes. Ci-cathepsin D gene expression was detected at 2h after treatment with Ci-TK, and elevated for up to 5h, and then slightly decreased. Gene expression of Ci-carboxypeptidase B1 and Ci-chymotrypsin was observed at 5h after treatment with Ci-TK, and then decreased. The enzymatic activities of Ci-cathepsin D, Ci-carboxypeptidase B1, and Ci-chymotrypsin showed similar alterations with 1-h lags. These gene expression and protease activity profiles verified that Ci-cathepsin D is initially activated, which is followed by the activation of Ci-carboxypeptidase B1 and Ci-chymotrypsin. Collectively, the present data suggest that Ci-TK directly induces Ci-cahtepsin D in test cells expressing Ci-TK receptor, leading to the secondary activation of Ci-chymotrypsin and Ci-carboxypeptidase B1 in the follicle in the tachykininergic oocyte growth pathway.
    Peptides 07/2011; 34(1):186-92. DOI:10.1016/j.peptides.2011.07.019 · 2.62 Impact Factor
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    • "HK-1 and the 10- amino-acid C-terminal sequence common to EKA and EKB (EKA/B) were also found to potently bind NK1–3, with the highest selectivity for NK1 (Page, 2004; Satake and Kawada, 2006a). In contrast, the putative TK-like peptides EKC and EKD show no binding to NK1–3 (Page, 2004; Satake and Kawada, 2006a). In protostomes, two types of TK-like peptides, invertebrate TKs and TK-related peptides (TKRPs), have been identified to date (Table 2). "
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    ABSTRACT: The critical phylogenetic position of ascidians leads to the presumption that neuropeptides and hormones in vertebrates are highly likely to be evolutionarily conserved in ascidians, and the cosmopolitan species Ciona intestinalis is expected to be an excellent deuterostome Invertebrate model for studies on neuropeptides and hormones. Nevertheless, molecular and functional characterization of Ciona neuropeptides and hormone peptides was restricted to a few peptides such as a cholecystokinin (CCK)/gastrin peptide, cionin, and gonadotropin-releasing hormones (GnRHs). In the past few years, mass spectrometric analyses and database searches have detected Ciona orthologs or prototypes of vertebrate peptides and their receptors, including tachykinin, insulin/relaxin, calcitonin, and vasopressin. Furthermore, studies have shown that several Ciona peptides, including vasopressin and a novel GnRH-related peptide, have acquired ascidian-specific molecular forms and/or biological functions. These findings provided indisputable evidence that ascidians, unlike other invertebrates (including the traditional protostome model animals), possess neuropeptides and hormone peptides structurally and functionally related to vertebrate counterparts, and that several peptides have uniquely diverged in ascidian evolutionary lineages. Moreover, recent functional analyses of Ciona tachykinin in the ovary substantiated the novel tachykininergic protease-assoclated oocyte growth pathway, which could not have been revealed in studies on vertebrates. These findings confirm the outstanding advantages of ascidians in understanding the neuroscience, endocrinology, and evolution of vertebrate neuropeptides and hormone peptides. This article provides an overview of basic findings and reviews new knowledge on ascidian neuropeptides and hormone peptides.
    ZOOLOGICAL SCIENCE 02/2010; 27(2):134-53. DOI:10.2108/zsj.27.134 · 0.86 Impact Factor
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