Journal of molecular endocrinology最新文献

{"title":"Hypothalamic neuropeptides as modulators of neural activity and behaviour.","authors":"Zoë M Ward, Karl J Iremonger","doi":"10.1530/JME-25-0209","DOIUrl":"10.1530/JME-25-0209","url":null,"abstract":"<p><p>Hypothalamic neural circuits control a diverse array of functions, including appetite, arousal, hormone secretion and social behaviour. Many of these functions and behaviours are expressed over long time windows, suggesting that long-lasting changes in neural activity are required. Neuropeptides are one class of neuromodulators that are highly expressed in the hypothalamus and are well suited to inducing long-lasting changes in excitability in neural circuits. Here, we review the role of hypothalamic neuropeptides in mediating long-lasting changes in neural states. These actions may allow neuropeptides to act as 'state controllers' that bridge the gap between transient sensory input and enduring changes in behaviour and neuroendocrine output.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147987434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Massively parallel functional genomic assays in endocrinology: from promise to delivery.","authors":"Jingxiang Xu, Vahid Aslanzadeh, Grzegorz Kudla, Robert K Semple","doi":"10.1530/JME-25-0134","DOIUrl":"10.1530/JME-25-0134","url":null,"abstract":"<p><p>The late 20th century saw major advances in mapping genes and mutations in endocrine disorders, driven by biochemical studies that identified defects endocrinologically and by family-based studies that mapped them genetically. In the 21st century, however, the world of genetics has been transformed by the mapping of the human genome and the development of next-generation sequencing technologies that allow genomes to be sequenced at population scale. This has led us to be swamped by a surfeit of information about genetic variation, with the so-called genetic 'variants of unknown significance' (VUS) greatly outnumbering pathogenic mutations in genes of clinical relevance. A revolution in functional genomics has since gathered pace, driven by the need to evaluate the function of rare genetic variants at scale. Recent advances in saturation mutagenesis enable the synthesis of libraries of thousands of gene variants. When coupled to increasingly creative use of a growing repertoire of downstream assays, this permits assessment of disease-relevant function of thousands of variants simultaneously. Such assays, widely known as multiplexed assays of variant effect (MAVEs), have major potential in endocrinology when applied to hormone receptors and their downstream signalling pathways. They help determine functional significance or otherwise of VUS, enable patient stratification for rare disease treatments, and yield new insights into structure-function relationships for target genes. We review the current state of development of MAVEs and their application to date to endocrine genetic disease, with particular reference to hormone receptors.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13250644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TSH promotes chemerin/CMKLR1-cAMP/ERK-DIO2 signaling in primary rat ependymal cells in vitro.","authors":"Xin Ning, Doudou Guo, Qing Huang, Cencen Wang, Yating Li, Yanfen Zhou, Xin Li","doi":"10.1530/JME-26-0028","DOIUrl":"10.1530/JME-26-0028","url":null,"abstract":"<p><strong>Abstract: </strong>In mammals, chemerin and its receptor CMKLR1 might be downstream effectors in response to a long photoperiod in the ependymal cells lining the third ventricle in rats. Iodothyronine deiodinase 2 (DIO2) is a main product of the involvement of TSH in photoperiodic signaling. Thus, the potential interplay of TSH and chemerin/CMKLR1 signaling might exist during photoperiodic changes. Our study aimed to investigate whether chemerin/CMKLR1 signaling could stimulate DIO2 production and how TSH could affect chemerin/CMKLR1 signaling in primary rat ependymal cells. Colocalization of chemerin with its receptor, CMKLR1, was observed using immunohistochemistry assay. The expression of chemerin and CMKLR1 was identified using real-time PCR and western blot analysis, respectively. DIO2 expression, which involves a dual signaling pathway (an increase in cAMP levels and phosphorylation of ERK1/2), was detected by western blot assay and enzyme-linked immunosorbent assay (ELISA). Our study showed the potential interaction between chemerin and CMKLR1 in primary rat ependymal cells. TSH could upregulate the expression of chemerin and CMKLR1 in chemerin-pretreated primary ependymal cells. In vitro treatment of primary ependymal cells with chemerin (10 ng/mL) or TSH (60 mIU/mL) could induce an increase in cAMP levels, ERK1/2 phosphorylation and DIO2 expression. Furthermore, we found that TSH could promote the effect of chemerin/CMKLR1 signaling on DIO2 production through an increase in cAMP levels and the phosphorylation of ERK1/2. We concluded that chemerin/CMKLR1 signaling could enhance DIO2 activity in primary rat ependymal cells in vitro, and this effect could be promoted by TSH through cAMP and phosphorylation of ERK1/2.</p><p><strong>Main points: </strong>Chemerin/CMKLR1 interaction in primary rat ependymal cells is discussed. Chemerin/CMKLR1 signals through cAMP and ERK phosphorylation to induce deiodinase 2 expression in primary ependymal cells. TSH promotes the effect of chemerin/CMKLR1 signaling on deiodinase 2 expression.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13239433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147930491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The molecular mechanism of melatonin in regulating osteoporosis based on the RANKL/OPG signaling axis.","authors":"Tai Guo, Junqing Jia, Dongsheng Hao, Peng Hu, Lin Sun","doi":"10.1530/JME-25-0220","DOIUrl":"10.1530/JME-25-0220","url":null,"abstract":"<p><p>Melatonin is a promising drug for improving bone mass in postmenopausal women. This study investigated the mechanism behind the regulation of melatonin on osteoblast differentiation. Mouse embryonic osteoblast precursor MC3T3-E1 cells were treated with melatonin or transfected with cathepsin D (CTSD) vectors. A cellular model was established by H2O2 treatment. Alkaline phosphatase (ALP) staining and Alizarin Red S staining were performed. An osteoporosis mouse model was established by ovariectomy (OVX) and treated with melatonin or transfected with a CTSD knockdown vector. Bone biomechanical testing was performed to assess bone strength. Histological bone damage was assessed, osteoclast differentiation was visualized using tartrate-resistant acid phosphatase staining, osteocalcin (OCN) and type I collagen α1 chain (COL1A1) expression was visualized using immunohistochemistry, and serum bone turnover markers procollagen type I N-propeptide (PINP) and C-terminal telopeptide of type I collagen (CTX-1) levels were measured using enzyme-linked immunosorbent assay. Receptor activator of NF-κB ligand (RANKL), osteoprotegerin (OPG), Wnt3a, and β-catenin protein levels were determined using western blotting. Melatonin treatment or CTSD overexpression promoted ALP activity and mineralization in MC3T3-E1 cells. Melatonin upregulated CTSD expression. Melatonin treatment enhanced bone strength, inhibited osteoclast differentiation, increased OCN and COL1A1 expression, elevated PINP levels, and reduced CTX-1 in OVX mice. Moreover, melatonin suppressed RANKL expression and promoted OPG, Wnt3a, and β-catenin expression. CTSD knockdown abolished the regulatory effects of melatonin on MC3T3-E1 cells and OVX mice. In conclusion, melatonin increases CTSD expression to promote osteoblast differentiation and regulate the RANKL/OPG/Wnt signaling pathway, thereby slowing down the progression of osteoporosis.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thyroglobulin and thyroglobulin antibodies in differentiated thyroid cancer: interpretation, challenges, and future perspectives.","authors":"M H Links, T P Links, W T Zandee, A C Muller Kobold","doi":"10.1530/JME-25-0217","DOIUrl":"10.1530/JME-25-0217","url":null,"abstract":"<p><p>Thyroglobulin (Tg) is a thyroid-specific protein playing a key role in thyroid hormone production. For patients with differentiated thyroid carcinoma (DTC), Tg is the main biomarker during follow-up determining treatment response and risk of disease recurrence. Accurate Tg measurement is complicated by assay-specific performance and interference, most notably thyroglobulin autoantibodies (TgAbs). High-sensitivity Tg assays can detect very low Tg levels, eliminating the need for TSH-stimulated Tg measurements. Because of potential TgAb interference in Tg assays, TgAb measurement must always accompany Tg analysis. TgAbs are present in a minority of healthy individuals, but in up to one-third of patients with DTC. While low-level TgAbs are often clinically irrelevant, higher titres interfere with Tg immunoassays, possibly causing false-negative Tg results. Importantly, TgAb trends themselves provide prognostic information: declining concentrations support remission, whereas rising titres may indicate recurrence, offering a potential useful surrogate marker when Tg is unreliable. Alternative and complementary laboratory strategies are emerging. Novel proteomic approaches may allow isoform-specific Tg detection, potentially distinguishing tumour-derived Tg from normal Tg. In parallel, liquid biopsy technologies, particularly cell-free DNA, circulating tumour DNA, and microRNA assays, are being explored for non-invasive detection of minimal residual disease, although their role in DTC remains to be defined. In summary, Tg and TgAbs remain the mainstay of laboratory monitoring in DTC. Their interpretation demands awareness of assay limitations, appropriate cut-offs, and the clinical context. Future integration of advanced proteomic and genomic biomarkers holds promise for more specific, individualized surveillance strategies in thyroid cancer.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13192691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating mechanistic models to decode the GnRH pulse generator in female mice.","authors":"Kateryna Nechyporenko, Deyana Ivanova, Xiao Feng Li, Krasimira Tsaneva-Atanasova, Margaritis Voliotis, Kevin T O'Byrne","doi":"10.1530/JME-25-0224","DOIUrl":"10.1530/JME-25-0224","url":null,"abstract":"<p><p>The gonadotrophin-releasing hormone (GnRH) pulse generator is a critical neural oscillator that governs reproductive function through the pulsatile release of luteinising hormone (LH) and follicle-stimulating hormone. Early electrophysiological studies, notably by Ernst Knobil, identified multiunit activity (MUA) volleys in the mediobasal hypothalamus that aligned with LH pulses, suggesting a neural basis for GnRH pulsatility. Although GnRH neurons exhibit some intrinsic secretory rhythmicity in vitro, their isolated electrophysiological signatures have proven inconsistent. Recent advances, including GCaMP fibre photometry in freely behaving mice, have revealed a precise correlation between episodic GnRH distal process activity and LH pulses. However, it is now well established that a neural oscillator comprising hypothalamic kisspeptin neurones co-expressing neurokinin B and dynorphin, collectively termed the KNDy network, represents the core construct of the GnRH pulse generator. Understanding the dynamics of this network and its modulation by external inputs, such as stress, metabolic cues and circadian rhythms, is essential. Computational modelling provides a systematic framework for integrating experimental data with mechanistic and predictive analyses to decode the GnRH pulse generator dynamics.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13150289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adsorption represents a critical challenge in the quantification of free 25-hydroxyvitamin D3.","authors":"Nick Narinx, Tom De Waal, Jennifer Afrakoma Nyamaah, Karel David, Joeri Walravens, Tom Fiers, Bruno Lapauw, Brigitte Decallonne, Frank Claessens, Jaak Billen, Dirk Vanderschueren, Pieter Vermeersch, Leen Antonio","doi":"10.1530/JME-25-0207","DOIUrl":"10.1530/JME-25-0207","url":null,"abstract":"<p><p>Equilibrium dialysis followed by liquid chromatography-tandem mass spectrometry is considered the gold standard for the isolation and quantification of free hormones. However, this technique has not been described for the analysis of free 25-hydroxyvitamin D3. This study investigated analytical challenges, focusing on stability and adsorption of 25-hydroxyvitamin D3 in aqueous buffer environments, to be considered prior to method development of equilibrium dialysis for free vitamin D. Experiments revealed that 25-hydroxyvitamin D3 is highly prone to adsorption, and to a minor extent degradation, resulting in severe analyte loss already upon introduction of 25-hydroxyvitamin D3 into the aqueous environment, far exceeding observations in serum where protein binding provides significant protection. While chemical degradation only slightly contributes, strong surface adsorption accounts for the majority of 25-hydroxyvitamin D3 loss observed. In contrast, the addition of methanol to the buffer environment completely mitigated analyte loss, confirming the severe adsorption of 25-hydroxyvitamin D3 to recipient surfaces. However, incorporating methanol as a buffer component fundamentally altered experimental conditions, thereby potentially disrupting the physiological equilibrium between 25-hydroxyvitamin D3, vitamin D-binding protein, and albumin, and by extension the free fraction of vitamin D. Consequently, the large extent of, primarily, adsorption of 25-hydroxyvitamin D3 in aqueous environments represents an important consideration in setting up equilibrium dialysis experiments for free vitamin D. These findings additionally highlight a critical need for novel analytical strategies that prevent adsorption while maintaining physiological equilibrium in the assessment of free vitamin D.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effect of pentoxifylline against high-glucose-induced ferroptosis in vascular smooth muscle cells.","authors":"Jing Zhou, Lijing Jiao, Siyao Jin, Yiwei Ran, Xian Meng, Lu Bai, Yanru Xi, Jing Wang, Zhansheng Zhao","doi":"10.1530/JME-25-0086","DOIUrl":"10.1530/JME-25-0086","url":null,"abstract":"<p><strong>Abstract: </strong>Ferroptosis has emerged as a pivotal form of regulated cell death implicated in diabetic vascular complications, yet the upstream transcriptional mechanisms governing this process remain insufficiently defined. Chronic hyperglycemia induces oxidative stress, iron overload, and vascular remodeling, but how these metabolic disturbances trigger ferroptotic signaling in vascular smooth muscle cells (VSMCs) remains unclear. In this study, we identify Krüppel-like factor 10 (KLF10) as a critical transcriptional mediator linking hyperglycemia to ferroptotic activation in VSMCs. High glucose increased KLF10 expression and enhanced its binding to the GPX4 promoter, leading to transcriptional repression of GPX4, heightened lipid peroxidation, and elevated reactive oxygen species. Pentoxifylline (PTX), a clinically used hemorheologic agent with antioxidant properties, significantly reduced ferroptosis-related lipid accumulation and partially restored GPX4 expression by suppressing KLF10 in vitro. In diabetic mice, PTX similarly attenuated dysregulation of the KLF10/GPX4 axis, lowered iron deposition, improved antioxidant enzyme activity, and mitigated vascular remodeling. Collectively, these findings establish the KLF10/GPX4 axis as a previously unrecognized regulator of diabetes-associated vascular ferroptosis and suggest that PTX may offer a promising therapeutic approach for limiting ferroptosis-driven vascular injury in diabetes.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147592818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SfE BES 2026: What's new in basic science endocrinology?","authors":"Gabriela da Silva Xavier","doi":"10.1530/JME-26-0062","DOIUrl":"10.1530/JME-26-0062","url":null,"abstract":"","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147674214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic-renal disease genetic architecture revealed by genomic structural equation modeling.","authors":"Kaixi Ding, Li Xiang, Wei Jiang, Ming Lei, Yongxiang Gao","doi":"10.1530/JME-25-0171","DOIUrl":"10.1530/JME-25-0171","url":null,"abstract":"<p><p>Physiologic mechanisms underlying metabolic and renal diseases interact and are highly comorbid, yet their genetic associations and underlying mechanisms have not been systematically elucidated. Using genome-wide association study (GWAS) summary statistics from UK Biobank, FinnGen, and CKDGen, we integrated and analyzed gout, serum urate, chronic kidney disease, kidney stones, and metabolic syndrome. Using genomic structural equation modeling (GSEM), we created the first genetic linkage map for 'gout-urate-kidney-metabolism' (GUKM) to explore shared genetic architecture. Post-GWAS analyses for GUKM-GSEM GWAS, including functional annotation, enrichment, fine-mapping, causal inference, and gsMap, identified key genetic loci, pathways, tissues/cell types, and potential drug targets. We identified 164 lead SNPs, including rs1260326 (chr2) and rs73607783 (chr8), with GSEA showing significant enrichment of GUKM-GSEM GWAS in cholesterol metabolism and lipid pathways (adjP < 0.05). Tissue and cell enrichment highlighted the liver, renal cortex, pancreas, proximal tubular epithelial cells, and hepatocytes (P < 0.05). Mendelian randomization indicated a potential causal role of GCKR (FDR < 0.05), which gsMap showed to be highly expressed in hepatocytes and liver tissue. The present study revealed the common genetic basis of metabolic and renal diseases and emphasized that lipid metabolism may be a key intermediary pathway connecting the 'metabolic-renal axis'. The liver, renal cortex, and pancreas were the primary enriched tissues, and GCKR was identified as a core gene and potential drug target. Overall, this study provides an important reference for the genetic mechanisms, key mechanisms, and intervention targets of related diseases.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147592875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}