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
    ​ white

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
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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
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    ABSTRACT: Activation of thyroxine by outer ring deiodination is the crucial first step of thyroid hormone action. Substrate-induced ubiquitination of type 2 deiodinase (D2) is the most rapid and sensitive mechanism known to regulate thyroid hormone activation. While the molecular machinery responsible for D2 ubiquitination has been extensively studied, the combination of molecular features sufficient and required to allow D2 ubiquitination remained to be determined. To address this question we constructed chimeric deiodinases by introducing different combinations of D2-specific elements into type 1 deiodinase (D1), another member of the deiodinase enzyme family, which however does not undergo ubiquitination in its native form. Studies on the chimeric proteins expressed transiently in HEK-293T cells revealed that combined insertion of the D2-specific instability loop and the K237/K244 D2 ubiquitin-carrier lysines into the corresponding positions of D1 could-not ubiquitinate D1 unless the chimera was directed to the endoplasmic reticulum (ER). Fluorescence resonance energy transfer measurements demonstrated that the C-terminal globular domain of the ER-directed chimera was able to interact with the E3 ligase subunit WSB1. However, this interaction did not occur between the chimera and the TEB4 E3 ligase although a native D2 could readily interact with the N-terminus of TEB4. In conclusion, insertion of the instability loop and ubiquitin-carrier lysines in combination with direction to the ER are sufficient and required to govern WSB1-mediated ubiquitination of an activating deiodinase enzyme.
    Journal of Molecular Endocrinology 07/2014; 53(2). DOI:10.1530/JME-14-0156
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    ABSTRACT: CD163-positive macrophages are highly expressed in the human adipose tissue (AT) particularly from obese individuals. Little is, however, known about the regulation of CD163 mRNA and the protein level of sCD163 in human AT. We aimed to examine the regulation of CD163 and sCD163 in AT. Human subcutaneous AT samples (n=5) were stimulated with dexamethasone (DEX; 200 nmol/L), lipopolysaccharide (LPS; 100 ng/mL), or DEX+LPS for various time periods up to 24 hours. Gene expressions of CD163, ADAM17, IL10, and TNFA were measured by RT-PCR. Protein levels of sCD163, IL-10, and TNF-α were measured by ELISA. Furthermore, AT was separated into the stromal and adipocyte fraction. We found that CD163 mRNA was strongly expressed in the stromal vascular fraction but hardly detectable in the isolated adipocytes. Incubating whole-AT with DEX significantly up-regulated CD163 (p<0.001), whereas, incubation with LPS had no effects on CD163 (p>0.05). In contrast, the protein level of sCD163 was not affected by DEX (p>0.05) but LPS significantly increased the level of sCD163 and TNF-α (p<0.05). This might be due to the concomitant LPS-stimulation of ADAM17, which is known to mediate shedding of the extracellular domains of sCD163 and TNF-α. Finally, DEX significantly reduced the LPS-induced TNF-α release to the incubation medium but had no effects on sCD163. We conclude that the expression of CD163 and the release of sCD163 are differentially regulated in human AT. Moreover, similar to studies on differentiated blood monocytes, TNF-α and sCD163 are concomitantly released in human AT by LPS, which also up-regulate ADAM17.
    Journal of Molecular Endocrinology 07/2014; 53(2). DOI:10.1530/JME-14-0089
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    ABSTRACT: Despite its identification over 100 years ago, new discoveries continue to add to the complexity of the regulation of the endocrine system. Today the nuclear receptors (NRs) that play such a pivotal role in the extensive communication networks of hormones and gene expression, remain an area of intense research. Orchestrating core processes from metabolism to organismal development, the gene expression programs they control are dependent on their cellular context, their own levels, and those of numerous co-regulatory proteins. A previously unknown component of these networks, non-coding RNAs (ncRNAs) are now recognized as potent regulators of NR signaling, impacting receptor and co-factor levels and function while being reciprocally regulated by the NRs themselves. This review explores the regulation enacted by microRNAs (miRNAs) and long ncRNAs (lncRNAs) on NR function, using representative examples to show the varied impacts of ncRNAs, in turn producing significant effects on the NR functional network in health and disease.
    Journal of Molecular Endocrinology 07/2014; 53(2). DOI:10.1530/JME-14-0134
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    ABSTRACT: Estrogens are essential for female reproduction and overall well-being, and estrogens in circulation are largely synthesized in ovarian granulosa cells. Using primary culture of ovarian granulosa cells from gonadotropin-primed immature rats, we recently uncovered that pituitary FSH and ovarian cytokine TGFβ1 induce calcineurin-mediated dephosphorylation-activation of CREB-regulated transcription coactivator (CRTC2) to modulate the expression of Star, Cyp11a1 and Hsd3b leading to increased progesterone production. This study explored the role of calcineurin and CRTC2 in FSH and TGFβ1 regulation of Cyp19a1 expression in granulosa cells. Ovarian granulosa cells given FSH had increased aromatase protein at 24 h post-treatment which subsided by 48 h, while TGFβ1 acting through its type I receptor augmented FSH action with a greater and longer effect. It is known that ovary-specific Cyp19a1 PII-promoter contains crucial response elements for CREB and nuclear receptors LRH-1/NR5A2 and SF-1/NR5A1, and Nr5a2 promoter also has a potential CREB-binding site. Here, we demonstrate FSH plus TGFβ1 increased LRH-1 and SF-1 protein, and their binding to Cyp19a1 PII-promoter evidenced by chromatin immunoprecipitation analysis. Moreover, pretreatment with calcineurin auto-inhibitory peptide (CNI) abolished the FSH+TGFβ1- but not FSH-upregulated aromatase activity at 48 h, and the corresponding mRNA changes of Cyp19a1, and Nr5a2 and Nr5a1 at 24 h. Additionally, FSH and TGFβ1 increased CRTC2 binding to Cyp19a1 PII-promoter and Nr5a2 promoter at 24 h with CREB bound constitutively. In all, this study implicates calcineurin and CRTC2 importantly mediate FSH and TGFβ1 collateral upregulation of Cyp19a1 expression together with its transcription regulators Nr5a2 and Nr5a1 in ovarian granulosa cells.
    Journal of Molecular Endocrinology 07/2014; 53(2). DOI:10.1530/JME-14-0048
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    ABSTRACT: Transcriptional coactivators have evolved as an important new class of functional proteins that participate with virtually all transcription factors and NRs to intricately regulate gene expression in response to a wide variety of environmental cues. Recent findings have highlighted that coactivators are important for almost all biological functions, and consequently, genetic defects can lead to severe pathologies. Drug discovery efforts targeting coactivators may prove valuable for treatment of a variety of diseases.
    Journal of Molecular Endocrinology 07/2014; 53(2). DOI:10.1530/JME-14-0080
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    ABSTRACT: The renin-angiotensin system (RAS) plays an important role in the pathophysiology of cardiovascular disorders (CVDs). Pharmacologic interventions targeting the RAS cascade has led to the discovery of renin inhibitors, angiotensin converting enzyme (ACE) inhibitors, and AT1 receptor blockers (ARBs) to treat hypertension and some cardiovascular and renal disorders. Mutagenesis and modeling studies have revealed that differential functional outcomes are the results of multiple active states conformed by the AT1 receptor upon interaction with angiotensin II (Ang II). The binding of agonist is dependent on both extracellular and intramembrane regions of the receptor molecule, and as a consequence occupies more extensive area of the receptor than a non-peptide antagonist. Both agonist and antagonist bind to the same intramembrane regions to interfere with each other's binding to exhibit competitive, surmountable interaction. The nature of interactions with the amino acids in the receptor is different for each of the ARBs given the small differences in the molecular structure between drugs. AT1 receptors attain different conformation states after binding various Ang II analogues, resulting in variable responses through activation of multiple signaling pathways. These include both classical and non-classical pathways mediated through growth factor receptor transactivations, and provide cross-communication between downstream signaling molecules. The structural requirements for AT1 receptors to activate extracellular signal-regulated kinases 1 and 2 through G proteins or G protein-independently through β-arrestin are different. We review the structural and functional characteristics of Ang II and its analogs and antagonists, and their interaction with amino acid residues in the AT1 receptor.
    Journal of Molecular Endocrinology 07/2014; 53(2). DOI:10.1530/JME-14-0125
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    ABSTRACT: Intrauterine growth restriction (IUGR) is a risk factor for obesity, particularly when offspring are born into an unrestricted nutritional environment. Herein we investigated the impact of IUGR and gender on circulating lipids and on adipogenic, lipogenic and adipokine gene expression in perirenal adipose tissue. Singleton lambs born to overnourished adolescent dams were normal birthweight (N) or IUGR (32% lower birthweight due to placental insufficiency). IUGR lambs exhibited increased fractional growth rates but remained smaller than N at necropsy (d77). At 48d, fasting plasma triglycerides, nonesterified fatty acids and glycerol were elevated predominantly in IUGR males. Body fat content was independent of prenatal growth but higher in females than males. In perirenal fat, relative to male lambs, females had larger adipocytes and lipoprotein lipase, fatty acid synthase and leptin mRNA expression levels were higher while IGF1, IGF2, IGF1R, IGF2R and hormone sensitive lipase mRNAs were lower, and all were independent of prenatal growth category; peroxisome-proliferator-activated receptor-γ and glycerol-3-phosphate dehydrogenase (G3PDH) mRNA expression were not affected by IUGR or gender. Adiposity indices were inversely related to G3PDH mRNA expression, and for the population as a whole the expression of IGF system genes in perirenal fat was negatively correlated with plasma leptin, fat mass and adipocyte size, and positively correlated with circulating IGF1. Higher plasma lipids in IUGR males may predict later adverse metabolic health and obesity, but in early postnatal life gender is the dominant influence on adipose tissue gene expression reflecting the already established sexual dimorphism in body composition.
    Journal of Molecular Endocrinology 06/2014; 53(1). DOI:10.1530/JME-14-0123