Neuron-restrictive silencer factor functions to suppress Sp1-mediated transactivation of human secretin receptor gene.

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The estrogen-related receptor alpha upregulates secretin expressions in response to hypertonicity and angiotensin II stimulation

Osmoregulation via maintenance of water and salt homeostasis is a vital process. In the brain, a functional secretin (SCT) and secretin receptor (SCTR) axis has recently been shown to mediate central actions of angiotensin II (ANGII), including initiation of water intake and stimulation of vasopressin (VP) expression and release. In this report, we provide evidence that estrogen-related receptor α (ERRα, NR3B1), a transcription factor mainly involved in metabolism, acts as an upstream activator of the SCT gene. In vitro studies using mouse hypothalamic cell line N-42 show that ERRα upregulates SCT promoter and gene expression. More importantly, knockdown of endogenous ERRα abolishes SCT promoter activation in response to hypertonic and ANGII stimulations. In mouse brain, ERRα coexpresses with SCT in various osmoregulatory brain regions, including the lamina terminalis and the paraventricular nucleus of the hypothalamus, and its expression is induced by hyperosmotic and ANGII treatments. Based on our data, we propose that both the upregulation of ERRα and/or the increased binding of ERRα to the mouse SCT promoter are two possible mechanisms for the elevated SCT expression upon hyperosmolality and central ANGII stimulation. © 2012 Lee et al.published_or_final_versio

Gonadotropin-releasing hormone: Regulation of the GnRH gene

As the key regulator of reproduction, gonadotropin-releasing hormone (GnRH) is released by neurons in the hypothalamus, and transported via the hypothalamo-hypophyseal portal circulation to the anterior pituitary to trigger gonadotropin release for gonadal steroidogenesis and gametogenesis. To achieve appropriate reproductive function, mammals have precise regulatory mechanisms; one of these is the control of GnRH synthesis and release. In the past, the scarcity of GnRH neurons and their widespread distribution in the brain hindered the study of GnRH gene expression. Until recently, the development of GnRH-expressing cell lines with properties similar to those of in vivo GnRH neurons and also transgenic mice facilitated GnRH gene regulation research. This minireview provides a summary of the molecular mechanisms for the control of GnRH-I and GnRH-II gene expression. These include basal transcription regulation, which involves essential cis-acting elements in the GnRH-I and GnRH-II promoters and interacting transcription factors, and also feedback control by gonadotropins and gonadal sex steroids. Other physiological stimuli, e.g. insulin and melatonin, will also be discussed. © 2008 The Authors.link_to_subscribed_fulltex

Metabolomics of Sarcopenia in Hong Kong Chinese

Session: Poster Session III: Presentation Number: MO0468Objective: Sarcopenia has recently been recognized as an independent condition by the International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM) Code. However, the pathophysiology of sarcopenia remains largely unknown. The aim of this study was to evaluate the role of metabolome in sarcopenia using untargeted metabolomics approach. Materials and methods: Untargeted metabolomic profiling in serum sample was performed in 287 participants from the Hong Kong Osteoporosis Study. In total, 725 metabolites with known identity and missingness<50% were included in the final analysis. The sarcopenia phenotypes, gait speed, handgrip strength, and appendicular lean mass (ALM), were studied. Multivariable linear regression was used to evaluate the association between metabolites and sarcopenia phenotypes. Multivariate analysis of covariance (MANCOVA) was used to evaluate the association of metabolite with multiple correlated quantitative sarcopenia phenotypes, with adjustment for age, sex, height, and weight. Pathway analysis was performed using MetaboAnalyst 3.0. Results: There were five, three, and one metabolites significantly associated with appendicular lean mass (ALM) measured using dual-energy X-ray absorptiometry, handgrip strength, and gait speed respectively with a false-discovery rate Q-value <0.05. The metabolite with the strongest association was creatine (Beta: +2.41kg per standard deviation [SD]), 3-methyl-2-oxobutyrate (Beta: +4.47kg per SD), and 5-hydroxylysine (Beta: -1.59ms-1 per SD) for ALM, handgrip strength, and gait speed, respectively. In MANCOVA analysis, 28 of the metabolites were significantly associated with the sarcopenia phenotype, two of which were further associated with fat mass. The variance explained by these 28 metabolites in handgrip strength, gait speed, ALM was 6.6%, 8.1%, and 10%, respectively. Conclusion: Our study identified muscle-related metabolites and demonstrated the power of a multivariate metabolomics approach

Identification of repressor element 1 in secretin/PACAP/VIP genes

Repressor element 1 (RE-1) is a negative, cis-acting regulatory element that interacts with the transcription factor RE-1-silencing transcription factor (REST). REST represses gene expression by two repressor domains that recruit other factors including mSin3 and CoREST. RE-1 has been identified in an increasing number of neuronal-specific genes, and recently, functional REST sites have also been discovered in VIP and PACAP genes. In the present article, we demonstrated for the first time that RE-1 sites are present in the 5′ flanking regions of several secretin/PACAP/VIP genes by in silico analysis. This observation suggests that RE-1/REST is a common negative regulatory pathway of this peptide family. © 2006 New York Academy of Sciences.link_to_subscribed_fulltex

Secretin: A putative neural and neurohypophysial factor regulating water homeostasis

State-of-the-Art Lecture: Neuropeptides and Peptidergic Neurons - Session 3 - Neuroendocrine neurones: paper no. S-4