Evolution of Parathyroid Hormone Receptor Family and Their Ligands in Vertebrate

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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

The Role of Endocrine G Protein-Coupled Receptors in Ovarian Cancer Progression

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Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

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

Insights into the evolution of proglucagon-derived peptides and receptors in fish and amphibians

Glucagon and the glucagon-like peptides (GLP-1 and GLP-2) share a common evolutionary origin and are triplication products of an ancestral glucagon exon. In mammals, a standard scenario is found where only a single proglucagon-derived peptide set exists. However, fish and amphibians have either multiple proglucagon genes or exons that are likely resultant of duplication events. Through phylogenetic analysis and examination of their respective functions, the proglucagon ligand-receptor pairs are believed to have evolved independently before acquiring specificity for one another. This review will provide a comprehensive overview of current knowledge of proglucagon-derived peptides and receptors, with particular focus on fish and amphibian species. © 2010 New York Academy of Sciences.link_to_subscribed_fulltex

Southwestern blotting in investigating transcriptional regulation

Southwestern blotting is used to investigate DNA-protein interactions. The advantage of this technique over other related methods such as electrophoretic mobility shift assay (EMSA) and DNA footprinting is that it provides information regarding the molecular weight of unknown protein factor. This method combines the features of Southern and Western blotting techniques; a denaturing SDS-PAGE is first employed to separate proteins electrophoretically based on size, and after transferring the proteins to a membrane support, the membrane-bound proteins are renatured and incubated with a 32P-labeled double-stranded oligonucleotide probe of specific DNA sequence. The interaction of the probe with the protein(s) is later visualized by autoradiography. This technique could be combined with database searching (TransFac, http://www.gene-regulation.com/pub/ databases.html#transfac), prediction of potential protein factors binding onto a target motif (e.g., Patch search), in vitro supershift EMSA and in vivo chromatin immunoprecipitation (ChIP) assays for effective identification of protein factors. The whole Southwestern blotting procedure takes ∼4 d to complete. In this article, a commonly used protocol and expected results are described and discussed.link_to_subscribed_fulltex

A functional variable number of tandem repeats is located at the 5′ flanking region of the human secretin gene plays a downregulatory role in expression

Secretin is a peptide hormone playing multiple functions in the brain-gut axis. In this report, we investigated, by promoter analysis, the potential function of the variable of tandem repeats (VNTR), located at the 5′ upstream region of the human secretin gene, and we demonstrated for the first time that this VNTR could downregulate transcription of the human secretin gene in a promoter-specific manner. The efficiency of VNTR in silencing the promoter was found to be directly related the number of repetitive units residing within. We also showed the deoxyribonucleic acid sequence as well as the length polymorphism of the VNTR of 76 Chinese individuals. These results collectively suggest that VNTR could potentially be a functional regulator to control the expression of the human secretin gene in different individuals. © 2008 Humana Press.link_to_subscribed_fulltex

Retinoic acid-induced human secretin gene expression in neuronal cells is mediated by cyclin-dependent kinase 1

Previously, we found that secretin transcript levels were induced by all-trans retinoic acid (RA) in a neuroblastoma cell model, SH-SY5Y. In this article, this RA-dependent upregulation process was further investigated. In the cyclin-dependent kinase 1 (Cdk1) inhibitor-treated cells, the RA-dependent induction of secretin gene expression was inhibited. Together with our previous works, we propose here that the RA responsiveness of the secretin promotor is mediated by two different pathways. The first pathway is by changing the expression levels of NFI-C and Sp proteins while the second pathway is by modifying the phosphorylation status of both NFI-C and Sp proteins via Cdk1. © 2006 New York Academy of Sciences.link_to_subscribed_fulltex