Abstract:
:Melanocortin 4 receptor (Mc4r/MC4R) is a G-Protein coupled receptor that is expressed in the hypothalamus and implicated in body weight control. Mutations in MC4R are the most frequent cause of monogenetic forms of human obesity. Despite its importance, the MC4R signaling pathways and transcriptional regulation underlying the melanocortin pathway are far from being fully understood. The transcription factor nescient helix-loop-helix 2 (Nhlh2) influences the melanocortin pathway through transcriptional regulation of prohormone convertase I, which influences the production of melanocortin peptides. In the present study, Nhlh2's role as a transcriptional regulator of Mc4r has been demonstrated. Nhlh2 knockout mice have reduced hypothalamic expression of Mc4r mRNA, suggesting that it could be a direct or indirect transcriptional regulator of the Mc4r promoter. To demonstrate direct transcriptional regulation, chromatin immunoprecipitation and electrophoretic gel shift assays show that Nhlh2 binds to the E-Boxes located at -551, -366 and +54 on the Mc4r promoter. Leptin-induced transactivation of the Mc4r promoter is significantly higher in the presence of exogenously added Nhlh2. siRNA knockdown of Nhlh2 leads to significantly reduced endogenous Mc4r mRNA expression levels in N29/2 cell line. Transactivation using promoters with mutations in each of the E-Boxes results in significantly reduced transactivation efficiency compared to the WT Mc4r promoter, suggesting that Nhlh2 regulates Mc4r transcription through these sites. Findings from these studies, combined with previous work implicating Nhlh2 as a transcriptional regulator of both the Mc4r gene and the melanocortin pathway, suggest that Nhlh2's transcriptional activity directly influences the human and rodent body weight control pathways.
journal_name
Mol Cell Endocrinoljournal_title
Molecular and cellular endocrinologyauthors
Wankhade UD,Good DJdoi
10.1016/j.mce.2011.05.022subject
Has Abstractpub_date
2011-07-20 00:00:00pages
39-47issue
1-2eissn
0303-7207issn
1872-8057pii
S0303-7207(11)00274-7journal_volume
341pub_type
杂志文章abstract::The objective of the study was to identify microRNAs (miRs) characteristic for follicular thyroid carcinoma (FTC) and to define their role in tumorigenesis. A miR-microarray study was conducted to identify miRs differentially expressed between FTCs and their surrounding tissues. Selection was further reinforced by a l...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2014.02.011
更新日期:2014-05-05 00:00:00
abstract::A central question in glucocorticoid mechanism of action via the glucocorticoid receptor (GR) is what determines ligand-selective transcriptional responses. Using a panel of 12 GR ligands, we show that the extent of GR phosphorylation at S226 and S211, GR half-life and transcriptional response, occur in a ligand-selec...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2010.06.007
更新日期:2010-10-07 00:00:00
abstract::Fibrosis is one of the key pathological features of airway remodeling in asthma. In the normal airway the amount of collagen and other extracellular matrix components is kept in equilibrium by regulation of synthesis and degradation. In asthma this homeostasis is disrupted due to genetic and environmental factors. In ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2012.01.007
更新日期:2012-04-04 00:00:00
abstract::Thyroid hormone (TH) modulates serum cholesterol by acting on TH receptor β1 (TRβ1) in liver to regulate metabolic gene sets. In rodents, one important TH regulated step involves induction of Cyp7a1, an enzyme in the cytochrome P450 family, which enhances cholesterol to bile acid conversion and plays a crucial role in...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2014.02.003
更新日期:2014-05-05 00:00:00
abstract::Best described outside the nervous system, caveolins are structural proteins that form caveolae, functional microdomains at the plasma membrane that cluster related signaling molecules. Caveolin-associated proteins include G protein-coupled receptors and G proteins, receptor tyrosine kinases, as well as protein kinase...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2008.04.005
更新日期:2008-08-13 00:00:00
abstract::The interaction between thyroid microsomal autoantibodies and thyroid microsomal antigen/thyroid peroxidase (TPO) has been studied using both intact antigen preparations and their water-soluble trypsin fragments. In an analysis of sera from 30 patients with Graves' or Hashimoto's diseases, microsomal antibodies showed...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(87)90187-0
更新日期:1987-09-01 00:00:00
abstract::The red-spotted grouper, Epinephelus akaara, is a protogynous hermaphroditic fish that shows the characteristic of natural sex change. In this study, 2-year-old female groupers were successfully reversed to functional males by oral administration of 17alpha-methyltestosterone (MT) for 42 days. The protein inhibitor of...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2009.04.015
更新日期:2009-10-15 00:00:00
abstract::The most widely conserved mammalian sperm antigen is sperm adhesion molecule 1, SPAM1/PH-20, which is also the major testicular hyaluronidase. This multifunctional glycosyl phosphatidylinositol (GPI)-linked protein plays several roles in fertilization and is encoded by a gene that resides among hyaluronidase family me...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2005.12.033
更新日期:2006-05-16 00:00:00
abstract::T3 effects on myosin heavy chain gene expression were analysed in muscles undergoing different fates during metamorphosis. Muscle fate was followed by somatic gene transfer of a constitutively expressed luciferase vector. Persistent expression was found in dorsal muscle which is remodelled during metamorphosis whilst ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(97)00110-x
更新日期:1997-08-08 00:00:00
abstract::Galectin-1 is highly expressed in blastocysts and trophoblast giant cells during implantation, and dysregulated galectin-1 is associated with many pregnancy-related abnormalities. Elevated galectin-1 contributes to cancer cells invasion. Here, we found that galectin-1 is expressed in mouse oocytes, preimplantation emb...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2017.11.003
更新日期:2018-07-15 00:00:00
abstract::Recent findings demonstrated that a subset of papillary thyroid cancers (PTCs) is characterized by reduced expression of the von Hippel-Lindau (VHL) tumor suppressor gene, and that lowest levels associated with more aggressive PTCs. In the present study, the levels of the two VHL mRNA splicing variants, VHL-213 (V1) a...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2017.01.019
更新日期:2017-03-05 00:00:00
abstract::It has been suggested that activation of mitochondrial respiration by thyroid hormone results in oxidative tissue injury secondary to increased reactive oxygen species production. In order to throw light on this subject, the effects of thyroid state on O2 consumption and H2O2 release by rat liver mitochondria were inv...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(02)00332-5
更新日期:2003-07-31 00:00:00
abstract::The oligosaccharide chains of pituitary glycoprotein hormones such as human thyroid-stimulating hormone (hTSH) have been shown to be important in biosynthesis, subunit association, secretion and bioactivity. However, the exact biological significance of these glycosylation variants (isoforms) remains controversial. Th...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(97)00136-6
更新日期:1997-09-19 00:00:00
abstract::Activation of the angiotensin II type 1 receptor (AT1R) is closely involved in the pathogenesis of cardiovascular disease. The human AT1R (hAT1R) mRNA splice variants have long 5'-untranslated regions (5'-UTRs) ranging from 272 to 414 bp that have the potential to form stable secondary structures. In this study, we sh...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2003.09.017
更新日期:2003-12-30 00:00:00
abstract::Accumulating evidence suggests that the human follitropin receptor is unusually sensitive to mutation. Previous results (Mol. Cell. Endo. 166 (2000) 101) determined that scanning mutations in a.a. 12-14 and 22-30 neither bound follitropin nor were present on the cell surface, suggesting that these regions are involved...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(02)00424-0
更新日期:2003-03-28 00:00:00
abstract::125I-glucagon was directly cross-linked to its receptor in isolated adipocyte plasma membranes using a UV irradiation procedure. This investigation resulted in identification of an adipocyte glucagon receptor complex of 62 kDa, present both in white and brown adipose tissues. The specificity of labeling was shown by i...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(94)90242-9
更新日期:1994-05-01 00:00:00
abstract::The activity of the hypothalamic-pituitary-adrenal (HPA) axis is characterized by an ultradian (pulsatile) pattern of hormone secretion. Pulsatility of glucocorticoids has been found critical for optimal transcriptional, neuroendocrine and behavioral responses. This review will focus on the mechanisms underlying the o...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2015.02.005
更新日期:2015-06-15 00:00:00
abstract::FOXL2 is a gene encoding a forkhead transcription factor. Its mutations or misregulation have been shown to cause the blepharophimosis-ptosis-epicanthus inversus (BPES) syndrome and more recently have been associated with the development of Ovarian Granulosa Cell Tumors (OGCT). BPES is a genetic disorder involving mil...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.mce.2011.06.019
更新日期:2012-06-05 00:00:00
abstract::The androgen receptor (AR), which mediates androgen action in the cell, belongs to the superfamily of nuclear receptors, a large group of transcription factors. Recent studies have described how the AR acts on specific target genes. The receptor's specificity of action depends on its regulation at different levels: ex...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/s0303-7207(02)00364-7
更新日期:2002-12-30 00:00:00
abstract::In a model of pulmonary hypertension induced by a single injection of monocrotaline (MCT), we observed a time-dependent right ventricular hypertrophy, which became apparent in treated rats 21 days after administration of MCT and progressed through day 45. Associated with this right ventricular hypertrophy were time-de...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(89)90011-7
更新日期:1989-04-01 00:00:00
abstract::MicroRNAs (miRNAs or miRs)-9 expression was reported to be upregulated in the follicular fluid of patients with polycystic ovary syndrome (PCOS). However, whether miR-9 affects ovarian dysfunction of PCOS and the related mechanisms are still unclear. Here we detected miR-9 and vitamin D receptor (VDR) expression in wo...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2019.02.012
更新日期:2019-04-15 00:00:00
abstract::A kallikrein-related protease was purified from rat ventral prostate cytosol by means of DEAE-Sepharose chromatography, followed by gel filtration on Sephadex G-100 and CM-cellulose chromatography. Antibodies raised in rabbits against the purified protease recognize two bands on immunoblots of prostatic cytosol: a 31,...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(89)90008-7
更新日期:1989-04-01 00:00:00
abstract::Parathyroid hormone-related protein (PTHrP) is produced by many tumors not associated with humoral hypercalcemia, including breast cancers. In this study, we used three human immortalized mammary epithelial cell lines that differ in tumorigenicity and PTHrP expression. Using RT-PCR we investigated 5' and 3' alternativ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(02)00298-8
更新日期:2003-06-30 00:00:00
abstract::We have previously shown that osteocalcin synthesis is readily induced by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in MG-63 human osteosarcoma cells (Mahonen et al. (1990) Biochim. Biophys. Acta 1048, 30-37). In the present study, the regulation of osteocalcin synthesis by other hormones of the steroid-thyroid hormone f...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(91)90269-x
更新日期:1991-04-01 00:00:00
abstract::Central leptin action requires PI3K activity to modulate glucose homeostasis and peripheral metabolism. However, the mechanism behind this phenomenon is not clearly understood. We hypothesize that hypothalamic PI3K activity is important for the modulation of the AMP-activated protein kinase (AMPK)/acetyl-CoA carboxyla...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2009.08.007
更新日期:2010-01-15 00:00:00
abstract::Brown fat has been highlight as a new therapeutic target for treatment of obesity and diabetes. However, molecular mechanism underlying brown adipogenesis are not fully understood. Here, we identified that MAP kinase phosphatase 3 (MKP3) has a novel role as regulator of brown adipocyte differentiation. The expression ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2015.08.023
更新日期:2015-11-15 00:00:00
abstract::Prostaglandin A1 (PGA1) increases heat shock element (HSE)-mediated transcription, thereby enhancing expression of HSE-bearing genes, including heat shock proteins. Because we recently found functional HSEs in the human and rodent c-fos promoters, we hypothesized that PGA1 might increase c-fos expression through the H...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(00)00241-0
更新日期:2000-06-01 00:00:00
abstract::In mammalian cells, the insulin receptor substrate 1 protein (IRS-1) is a specific substrate for insulin and IGF-1 receptor tyrosine kinases which is involved in mediating metabolic and mitogenic actions of insulin and IGFs. In order to determine if IRS-1 is also essential in a chicken derived hepatoma cell line (LMH ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(97)00245-1
更新日期:1998-02-01 00:00:00
abstract::The main objective of this study was to characterize nuclear T3 and T4 binding in the developing rat brain. More specifically, we sought to determine (a) whether T3 and T4 bind to the same nuclear receptor, (b) whether there are multiple forms of nuclear T3 or T4 receptors, and (c) whether the above parameters are sim...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(83)90158-2
更新日期:1983-08-01 00:00:00
abstract::Several lines of evidence indicate that the number of GnRH receptors (GnRH-R) and therefore, gonadotrope responsiveness to GnRH, is highly dependent upon the level of GnRH-R mRNA. To explore this aspect of regulation, we have isolated a 3.3 kb fragment encompassing the promoter region of the rat GnRH-R gene. Primer ex...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(98)00149-x
更新日期:1998-09-25 00:00:00