Journal of Molecular Endocrinology Impact Factor & Information

Publisher: Society for Endocrinology, BioScientifica

Journal description

Journal of Molecular Endocrinology focuses specifically on endocrinology research at the cellular and molecular level, thus complementing Journal of Endocrinology.

Current impact factor: 3.08

Impact Factor Rankings

2015 Impact Factor Available summer 2016
2014 Impact Factor 3.081
2013 Impact Factor 3.621
2012 Impact Factor 3.577
2011 Impact Factor 3.485
2010 Impact Factor 3.628
2009 Impact Factor 3.221
2008 Impact Factor 3.225
2007 Impact Factor 2.801
2006 Impact Factor 2.988
2005 Impact Factor 2.474
2004 Impact Factor 3.855
2003 Impact Factor 3.701
2002 Impact Factor 4.359
2001 Impact Factor 3.649
2000 Impact Factor 2.654
1999 Impact Factor 2.331
1998 Impact Factor 1.88
1997 Impact Factor 1.856
1996 Impact Factor 2.381
1995 Impact Factor 2.727
1994 Impact Factor 2.232
1993 Impact Factor 1.946
1992 Impact Factor 2.156

Impact factor over time

Impact factor

Additional details

5-year impact 3.44
Cited half-life 8.20
Immediacy index 0.73
Eigenfactor 0.01
Article influence 1.10
Website Journal of Molecular Endocrinology website
Other titles Journal of molecular endocrinology (Online), JME
ISSN 0952-5041
OCLC 44451537
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details


  • Pre-print
    • Author cannot archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • 12 months embargo
  • Conditions
    • In any repository
    • Publisher's version/PDF cannot be used
    • Set statement to accompany deposit (see policy)
    • Publisher last contacted on 18/04/2013
  • Classification

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: TMEFF2 is a transmembrane protein with unknown function, containing an altered epidermal growth factor (EGF)-like motif, two follistatin-like domains, and a cytosolic tail with a putative G-protein-activating motif. TMEFF2 is predominantly expressed in brain and prostate and has been implicated in cell signaling, neuronal cell survival, and tumor suppression. We found that expression of TMEFF2 in pituitary corticotrope cells inhibits the effects of corticotropin-releasing hormone (CRH) on the production of intracellular cAMP, and CREB, and transcription of Pomc. Regulation of the activity of CRH by TMEFF2 requires neither the cytoplasmic tail nor the EGF domain, while deletion of the follistatin modules abolishes the inhibitory function of TMEFF2. Moreover, a soluble secreted protein containing the complete extracellular domain is sufficient for inhibition of CRH signaling. TMEFF2-induced inhibition depends on serum components. Furthermore, TMEFF2 regulates the non-canonical activin/BMP4 signaling, PI3K, and Ras/ERK1/2 pathways. Thus, TMEFF2 inhibits the CRH signaling pathway and the PI3K/AKT and Ras/ERK1/2 pathways, contributing to a significant inhibition of transcription of Pomc. We found that expression of TMEFF2 in human Cushing's adenoma is reduced when compared with normal human pituitary, which may indicate that TMEFF2 acts as a tumor suppressor in these adenomas. Furthermore, the overexpression of TMEFF2 decreased proliferation of corticotrope cells. Our results indicate a potential therapeutic use of TMEFF2 or factors that stimulate the activity of TMEFF2 for the treatment of corticotrope tumors in order to reduce their secretion of ACTH and proliferation. © 2015 Society for Endocrinology.
    Journal of Molecular Endocrinology 12/2015; 54(1):51-63. DOI:10.1530/JME-14-0225

  • Journal of Molecular Endocrinology 12/2015; 55(3):263-275. DOI:10.1530/JME-15-0076

  • Journal of Molecular Endocrinology 12/2015; 55(3):169-181. DOI:10.1530/JME-15-0101

  • Journal of Molecular Endocrinology 12/2015; 55(3):E1-E2. DOI:10.1530/JME-15-0236
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    ABSTRACT: The generation of therapeutic β-cells from human pluripotent stem cells relies on the identification of growth factors that faithfully mimic pancreatic β-cell development in vitro. In this context, the aim of the study was to determine the expression and function of the Glial cell line derived neurotrophic factor receptor α 3 (GFRα3) and its ligand Artemin in islet cell development and function. GFRα3 and Artn expression were characterized by in situ hybridization, immunochemistry and qRT-PCR. We used GFRα3-deficient mice to study GFRα3 function and generated a transgenic mice overexpressing Artn in the embryonic pancreas to study Artn function. We found that GFRα3 is expressed at the surface of a subset of Ngn3-positive endocrine progenitors as well as of embryonic α- and β-cells, while Artn is found in the pancreatic mesenchyme. Adult β-cells lack GFRα3 but α-cells express the receptor. GFRα3 was also found in parasympathetic and sympathetic intra islets neurons as well as in glial cells in the embryonic and adult pancreas. The loss of GFRα3 or overexpression of Artn has no impact on Ngn3- and islet- cells formation and maintenance in the embryo. Islet organisation and innervation as well as glucose homeostasis is normal in GFRα3-deficient mice suggesting functional redundancy.
    Journal of Molecular Endocrinology 11/2015; DOI:10.1530/JME-15-0213
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    ABSTRACT: The H295R adrenocortical cell line is widely used for molecular analysis of adrenal functions but is known to have only modest ACTH responsiveness. The lack of ACTH response was linked to low expression of its receptor, melanocortin 2 receptor (MC2R). We hypothesized that increasing MC2R accessory protein (MRAP), which is required to traffic MC2R from the endoplasmic reticulum to the cell surface, would increase ACTH responsiveness. Lentiviral particles containing human MRAP-open reading frame were generated and transduced in H295R cells. Using antibiotic resistance, eighteen clones were isolated for characterization. The most ACTH-responsive steroidogenic clone, H295RA, was used for further experiments. Successful induction of MRAP and increased expression of MC2R in H295RA cells was confirmed by quantitative real time RT-PCR and western blotting. Treatment with ACTH significantly increased aldosterone, cortisol, and dehydroepiandrosterone production in H295RA cells. ACTH also significantly increased transcript levels for all the steroidogenic enzymes required to produce aldosterone, cortisol, and dehydroepiandrosterone, as well as MC2R mRNA. Further analysis using liquid chromatography/tandem mass spectrometry revealed that the main unconjugated steroids produced in H295RA cells were 11-deoxycortisol, cortisol, and androstenedione. Treatment of H295RA cells with ACTH also acutely increased cAMP production and cellular protein levels for total and phosphorylated steroidogenic acute regulatory protein. In summary, through genetic manipulation, we have developed an ACTH-responsive human adrenocortical cell line. The cell line will provide a powerful in vitro tool for molecular analysis of physiologic and pathologic conditions involving the hypothalamic-pituitary-adrenal axis.
    Journal of Molecular Endocrinology 11/2015; DOI:10.1530/JME-15-0230
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    ABSTRACT: G protein-coupled receptor 120 (GPR120), an adipogenic receptor critical for the differentiation and maturation of adipocytes, plays an important role in controlling obesity in both humans and rodents, and thus is an attractive target of obesity treatment studies. However, the mechanisms that regulate the expression of porcine GPR120 remain unclear. In this study, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) techniques were used to analyze and identify the binding of C/EBPβ (transcription factor CCAAT/enhancer binding protein beta) to the GPR120 promoter. C/EBPβ overexpression and RNA interference studies showed that C/EBPβ regulated GPR120 promoter activity and endogenous GPR120 expression. The binding site of C/EBPβ in GPR120 promoter region from -101 to -87 was identified by promoter deletion analysis and site-directed mutagenesis. Overexpression of C/EBPβ increased endogenous GPR120 expression in pig kidney cells (PK). Furthermore, when endogenous C/EBPβ was knocked down, GPR120 mRNA and protein levels were decreased. The stimulatory effect of C/EBPβ on GPR120 transcription and its ability to bind the transcription factor binding site were confirmed by luciferase, ChIP and EMSA. Moreover, the mRNA and protein expression levels of C/EBPβ were induced by high fat diet-feeding. Taken together, it can be concluded that C/EBPβ plays a vital role in regulating GPR120 transcription, and suggest HFD-feeding induces GPR120 transcription by influencing C/EBPβ expression.
    Journal of Molecular Endocrinology 11/2015; DOI:10.1530/JME-15-0200
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    ABSTRACT: Inability of pancreatic β-cells to make sufficient insulin to control blood sugar is a central feature of the aetiology of most forms of diabetes. In this review we focus on the deleterious effects of oxidative stress and ER stress on β-cell insulin biosynthesis and secretion, and on inflammatory signalling and apoptosis with a particular emphasis on type 2 diabetes. We argue that oxidative stress and ER stress are closely entwined phenomenon fundamentally involved in β-cell dysfunction, by direct effects on insulin biosynthesis and due to consequences of the ER stress-induced unfolded protein response. We summarise evidence that, although these phenomenon can be driven by intrinsic β-cell defects in rare forms of diabetes, in type 2 diabetes β-cell stress is driven by a range of local environmental factors including increased drivers of insulin biosynthesis, glucolipotoxicity and inflammatory cytokines. We describe our recent findings that a range of inflammatory cytokines contribute to β-cell stress in diabetes, and our discovery that IL-22 protects β-cells from oxidative stress regardless of the environmental triggers, and can correct much of diabetes pathophysiology in animal models. Finally we summarise evidence that β-cell dysfunction is reversible in type 2 diabetes, and discuss therapeutic opportunities for relieving oxidative and ER stress and restoring glycaemic control.
    Journal of Molecular Endocrinology 11/2015; DOI:10.1530/JME-15-0232
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    ABSTRACT: The arcuate-nucleus of the hypothalamus is essential for metabolic-homeostasis and responds to leptin by producing several neuropeptides including proopiomelanocortin (POMC). We previously reported that high-dose erythropoietin (Epo)-treatment in mice while increasing hematocrit, reduced body-weight, fat-mass, and food intake, and increased energy-expenditure. Moreover, we showed that mice with Epo receptor (EpoR) restricted to erythroid cells (ΔEpoRE) became obese and exhibited decreased energy-expenditure. Epo/EpoR-signaling was found to promote hypothalamus POMC-expression independently from leptin. Herein we used wild-type (WT) and ΔEpoRE-mice and hypothalamus-derived neural-culture system to study the signaling pathways activated by Epo in POMC neurons. We show that Epo-stimulation activated STAT3-signaling and up-regulated POMC expression in WT neural cultures. ΔEpoRE-mice hypothalamus showed reduced POMC levels, and lower STAT3-phosphorylation, with and without leptin-treatment, compared to in vivo and ex vivo WT controls. Collectively, these data show that Epo regulates hypothalamus POMC-expression via STAT3-activation, and provide a previously unrecognized link between Epo- and leptin-response.
    Journal of Molecular Endocrinology 11/2015; DOI:10.1530/JME-15-0171
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    ABSTRACT: Expression of the G protein subunit Goα has been shown to be prominent in the atria of the rat heart and to be significantly associated with atrial natriuretic factor (ANF)-containing atrial-specific secretory granules by immunocytochemistry. In addition, differential expression profile analysis using oligonucleotide arrays has shown that the Goα isoform 1 (Goα1) is 2.3-fold more abundant in the atria than it is in the ventricles. In the present report, we show protein-protein interaction between Goα and ANF by yeast two-hybrid and by immunoprecipitation. A cardiac conditional Goα knockout model developed for the present study showed a 90% decrease in Goα expression and decreased atrial expression and ANF and brain natriuretic peptides (BNP) content. Expression of chromogranin A, a specific atrial granule core constituent, was not affected. Morphometric assessment of atrial tissue showed a very significant decrease in atrial-specific granule density as well as granule core electron density. Atrial electrical activity was not affected. The results obtained are compatible with the suggestion that Goα plays a role in ANF sorting during intracellular vectorial transport and with the presence of a mechanism that preserves the molar relationship between cellular ANF and BNP stores in the face of the decreased production of these hormones.
    Journal of Molecular Endocrinology 05/2015; 54(3):277-288. DOI:10.1530/JME-15-0081
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    ABSTRACT: The monocarboxylate transporter 8 (MCT8) is a member of the major facilitator superfamily (MFS). These membrane-spanning proteins facilitate translocation of a variety of substrates, MCT8 specifically transports iodothyronines. Mutations in MCT8 are the underlying cause of severe X-linked psychomotor retardation. At the molecular level, such mutations led to deficiencies in substrate translocation due to reduced cell-surface expression, impaired substrate binding, or decreased substrate translocation capabilities. However, the causal relationships between genotypes, molecular features of mutated MCT8, and patient characteristics have not yet been comprehensively deciphered. We investigated the relationship between pathogenic mutants of MCT8 and their capacity to form dimers (presumably oligomeric structures) as a potential regulatory parameter of the transport function of MCT8. Fourteen pathogenic variants of MCT8 were investigated in vitro with respect to their capacity to form oligomers. Particular mutations close to the substrate translocation channel (S194F, A224T, L434W, and R445C) were found to inhibit dimerization of MCT8. This finding is in contrast to those for other transporters or transmembrane proteins, in which substitutions predominantly at the outer-surface inhibit oligomerization. Moreover, specific mutations of MCT8 located in transmembrane helix 2 (del230F, V235M, and ins236V) increased the capacity of MCT8 variants to dimerize. We analyzed the localization of MCT8 dimers in a cellular context, demonstrating differences in MCT8 dimer formation and distribution. In summary, our results add a new link between the functions (substrate transport) and protein organization (dimerization) of MCT8, and might be of relevance for other members of the MFS. Finally, the findings are discussed in relationship to functional data combined with structural-mechanistical insights into MCT8. © 2015 Society for Endocrinology.
    Journal of Molecular Endocrinology 02/2015; 54(1):39-50. DOI:10.1530/JME-14-0272
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    ABSTRACT: The mineralocorticoid receptor (MR) is a member of the nuclear receptor superfamily. Pathological activation of the MR causes cardiac fibrosis and heart failure, but clinical use of MR antagonists is limited by the renal side effect of hyperkalemia. Coregulator proteins are known to be critical for nuclear receptor-mediated gene expression. Identification of coregulators which mediate MR activity in a tissue-specific manner may allow the development of novel tissue-selective MR modulators that confer cardiac protection without adverse renal effects. Our earlier studies identified a consensus motif amongst MR-interacting peptides, MPxLxxLL. Gem-associated protein 4 (Gemin4) is one of the proteins which contains this motif. Transient transfection experiments in HEK293 and H9c2 cells demonstrated that Gemin4 repressed agonist-induced MR transactivation in a cell-specific manner. Furthermore, overexpression of Gemin4 significantly decreased, while knockdown of Gemin4 increased, the mRNA expression of specific endogenous MR target genes. A physical interaction between Gemin4 and MR is suggested by their nuclear co-localisation upon agonist treatment. These findings indicate that Gemin4 functions as a novel coregulator of the MR.
    Journal of Molecular Endocrinology 01/2015; 54(2). DOI:10.1530/JME-14-0078
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    ABSTRACT: The role of the highly-conserved 'DRY' motif in the signaling of the CB1 cannabinoid receptor (CB1R) was investigated by introducing single, double and triple alanine mutations into this site of the receptor. We found that the CB1R-R3.50A mutant displays a partial decrease in its ability to activate heterotrimeric Go proteins (~85% of wild-type CB1R (CB1R-WT)). Moreover, this mutant showed impaired β-arrestin binding in response to agonist stimulus, although its basal β-arrestin binding was enhanced. More strikingly, the double mutant CB1R-D3.49A/R3.50A was biased toward β-arrestins, as it gained a robustly increased β-arrestin1 and β-arrestin2 binding ability compared to the wild-type receptor, while its G protein activation was decreased. In contrast, the double mutant CB1R-R3.50A/Y3.51A proved to be G protein-biased, as it was practically unable to recruit β-arrestin2 in response to agonist stimulus, while still activating G proteins, although at a reduced level (~75% of CB1R-WT). Agonist-induced ERK1/2 activation of the CB1R mutants showed good correlation with their β-arrestin binding ability but not with their G protein activation or inhibition of cAMP accumulation. Our results suggest that G protein-activation and β-arrestin-binding of the CB1R are mediated by distinct receptor conformations and the conserved 'DRY' motif plays different roles in the stabilization of these conformations, thus mediating both G protein- and β-arrestin2-mediated functions of CB1R.
    Journal of Molecular Endocrinology 12/2014; 54(1). DOI:10.1530/JME-14-0219
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    ABSTRACT: MicroRNAs have been implicated in a variety of physiological processes, however, the function of miRNAs in insulin secretion and type 2 diabetes is still unclear. Stxbp1 plays an essential role in exocytosis, and is crucial for insulin secretion. In this study, we focused on the molecular mechanism of Stxbp1 in insulin secretion by identifying its upstream regulators: miR-218 and miR-322. The Stxbp1 expression was significantly increased in isolated mouse islets exposed to high glucose within 1 hour; while 2 of its predicted upstream miRNAs were found to be down-regulated. Further study found that miR-218 and miR-322 directly interact with Stxbp1 by target the 3'UTR of its mRNA. MIN6 cells overexpressed with the two miRNAs showed a sharp decline in insulin secretion and a decreased sensitivity to glucose; while the inhibition of the two miRNAs promoted insulin secretion. However, islets treated with prolonged high glucose, which is known as glucolipotoxicity, displayed relatively high expression of miR-218 and miR-322, and a reduced level of Stxbp1 accompanied with the block of insulin secretion. In summary, this study identified the pathway consisting of miR-218/322 and Stxbp1 in insulin secretion, contributing to the miRNA-implicated network of beta-cell function.
    Journal of Molecular Endocrinology 12/2014; 54(1). DOI:10.1530/JME-14-0305
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    ABSTRACT: Diabetes can be managed by careful monitoring of blood glucose and timely delivery of exogenous insulin. However, even with fastidious compliance, people with diabetes can suffer from numerous complications including atherosclerosis, retinopathy, neuropathy, and kidney disease. This is because delivery of exogenous insulin coupled with glucose monitoring cannot provide the fine level of glucose control normally provided by endogenous β-cells in the context of intact islets. Moreover, a subset of people with diabetes lack awareness of hypoglycemic events; a status that can have grave consequences. Therefore, much effort has been focused on replacing lost or dysfunctional β-cells with cells derived from other sources. The advent of stem cell biology and cellular reprogramming strategies have provided impetus to this work and raised hopes that a β-cell replacement therapy is on the horizon. In this review, we look at two components that will be required for successful β-cell replacement therapy: a reliable and safe source of β-cells and a mechanism by which such cells can be delivered and protected from host immune destruction. Particular attention is paid to insulin-producing cells derived from pluripotent stem cells because this platform addresses the issue of scale, one of the more significant hurdles associated with potential cell-based therapies. We also review methods for encapsulating transplanted cells, a technique that allows grafts to evade immune attack and survive for a long term in the absence of ongoing immunosuppression. In surveying the literature, we conclude that there are still several substantial hurdles that need to be cleared before a stem cell-based β-cell replacement therapy for diabetes becomes a reality.
    Journal of Molecular Endocrinology 12/2014; 53(3):R119-R129. DOI:10.1530/JME-14-0188
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    ABSTRACT: The proteolysis of the pro-opiomelanocortin precursor results in the formation of melanocortins (MCs), a group of peptides that share the conserved -H-F-R-W- sequence, which acts as a pharmacophore for five subtypes of melanocortin receptors (MCRs). Melanocortin type 2 receptor (MC2R; also known as ACTHR) is the most specialized of all the MCRs. It is predominantly expressed in the adrenal cortex and specifically binds ACTH. Unlike other MCRs, it requires MRAP1 for formation of active receptor and for its transport to the cell membrane. The molecular mechanisms underlying this specificity remain poorly understood. In this study, we used directed mutagenesis to investigate the role of various short MC2R sequence segments on receptor membrane trafficking and specific activation upon stimulation with ligands. The strategy of the study was to replace 2-5 amino acid residues within one MC2R segment with the corresponding residues of MC4R. In total, 20 recombinant receptors C-terminally fused to enhanced green fluorescent protein were generated and their membrane trafficking efficiencies and cAMP response upon stimulation with -MSH and ACTH(1-24) were estimated during their stand-alone expression and co-expression with MRAP1-. Our results indicate that both the motif that determines the ligand-recognition specificity and the intracellular retention signal are formed by a specific extracellular structure, which is supported by the correct alignment of the transmembrane. Our results also suggest that the aromatic-residue-rich segment of extracellular loop 2 is involved in the effects mediated by the second ACTH pharmacophore (-K-K-R-R-).
    Journal of Molecular Endocrinology 07/2014; 53(2). DOI:10.1530/JME-14-0169