Journal of molecular endocrinology最新文献

{"title":"Contrasting roles for GLP-1R and GIPR in a model of diet-induced obesity.","authors":"Jie Gao, Shelby Cree, Seungmin Ham, Cameron Nowell, Alex Parker, Peishen Zhao, Lynda Whiting, Kyle W Sloop, Ricardo J Samms, Patrick M Sexton, Denise Wootten, Dana S Hutchinson","doi":"10.1530/JME-25-0053","DOIUrl":"10.1530/JME-25-0053","url":null,"abstract":"<p><p>The glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) are important incretin receptors that are therapeutic targets for the treatment of type 2 diabetes and obesity. This study extensively characterised the metabolic phenotype of mice with global deletion of either the GLP-1R or GIPR side by side under identical conditions. Age-matched male wild-type (WT) C57Bl6NTac, GLP-1RKO or GIPRKO mice were placed on a high-fat or chow diet for 12 weeks, and a range of in vivo (weight gain, food intake, glucose tolerance, insulin tolerance, and whole-body energy metabolism) and ex vivo (white adipocyte lipolysis, brown adipose tissue and liver mitochondrial function, adipocyte and islet size, and hepatic steatosis) parameters were measured. While both WT and GLP-1RKO mice gained weight similarly on a HFD, obese high-fat-fed GLP-1RKO mice had altered glucose and insulin tolerance, and exhibited hepatic steatosis, highlighting the physiological importance of the GLP-1R in the regulation of blood glucose and lipid homoeostasis. In contrast, GIPRKO mice were partially resistant to diet-induced obesity compared to the WT mice, which was associated with a small reduction in food intake and intact epididymal and subcutaneous white adipocyte β-adrenoceptor-mediated lipolysis. Similarly, WT mice treated with a GIPR antagonist prevented weight gain due to a reduction in food intake on a HFD. These findings provide further support that the GLP-1R is important for normal glycaemic control, whereas the GIPR may play a role in the regulation of body weight.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033600","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":"Capsaicin-activated autophagy protects BMSC function under oxidative stress: mechanisms and therapeutic implications.","authors":"Yurong Chen, Qian Peng, Dongmei Lan, Chao Yao, Xiang Chen, Yan Wang, Shengcai Qi","doi":"10.1530/JME-25-0063","DOIUrl":"10.1530/JME-25-0063","url":null,"abstract":"<p><p>Bone marrow stromal cells (BMSCs) play an important role in bone regeneration, but their functional activity is affected by oxidative stress, which is a key pathological feature of osteoporosis. The aim of this study was to investigate the effects of capsaicin on the proliferation and differentiation of BMSCs under oxidative stress. We assessed cell viability and osteogenic potential of capsaicin in promoting BMSC survival and enhancing osteogenic capacity under oxidative stress by cell counting kit-8 (CCK-8), reactive oxygen species fluorescence staining, alkaline phosphatase (ALP) staining, Alizarin Red S (ARS) staining, Western blot (WB), and real-time PCR (RT-PCR). Our results indicate that capsaicin improves cell viability, antioxidant capacity, and osteogenic differentiation in rat BMSCs treated with hydrogen peroxide (H2O2). In addition, immunohistochemistry (IHC) analysis revealed that the surface of BMSCs expressed the capsaicin receptor transient receptor potential vanilloid protein 1 (TRPV1). More importantly, capsaicin increased Ca2+ influx and autophagy and inhibited phosphorylation of the PI3K/AKT/mTOR signaling pathway. In conclusion, capsaicin protects BMSC function during oxidative stress, possibly through inducing TRPV1-mediated Ca2+ influx and PI3K/AKT/mTOR-activated autophagy. The results suggest the potential of capsaicin as a therapeutic agent for osteoporosis.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075443","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":"Aldosterone synthase inhibition: a novel bullet to fight cardiovascular-kidney-metabolic syndrome.","authors":"Jonatan Barrera-Chimal, Anand Vaidya, Frederic Jaisser","doi":"10.1530/JME-25-0047","DOIUrl":"10.1530/JME-25-0047","url":null,"abstract":"<p><p>Aldosterone is synthesized by the CYP11B2 enzyme, primarily in the zona glomerulosa of the adrenal gland. It exerts its classical effects on sodium and water balance in the renal distal nephron through binding to the mineralocorticoid receptor (MR). Excess aldosterone production or overactivation of the MR outside the distal nephron leads to cardiac, renal, and vascular injury by increasing oxidative stress and activating the inflammatory and fibrotic pathways. MR antagonists (MRAs) have proved effective at decreasing organ damage and the deleterious effects of excess aldosterone/MR activation. However, MRAs do not fully block the non-genomic effects of aldosterone, which may contribute to residual risks. CYP11B2 inhibition has emerged as an additional therapeutic approach to decreasing the deleterious genomic and non-genomic effects of aldosterone. The development of specific aldosterone synthase inhibitors (ASi) has proved challenging due to the considerable similarity between aldosterone synthase and 11β-hydroxylase, an enzyme encoded by the CYP11B1 gene that catalyzes cortisol synthesis. In this review, we summarize the latest developments on preclinical evidence and clinical trials for ASi and explore the potential clinical advantages of ASi.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006298","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":"Impact of Parabacteroides distasonis colonization on host microbiome, metabolome, immunity, and diabetes onset.","authors":"Khyati Girdhar, Audrey Randall, Keiichiro Mine, Clarissa Howard, Alessandro Pezzella, Dogus Dogru, Lukas Rhodes, Brady James, Umesh K Gautam, Dagmar Šrůtková, Tomas Hudcovic, Juan J Aristizabal-Henao, Michael Kiebish, Emrah Altindis","doi":"10.1530/JME-25-0025","DOIUrl":"10.1530/JME-25-0025","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) is caused by autoimmune destruction of pancreatic β-cells. The insulin B-chain 9-23 (insB9-23) peptide is a critical epitope in triggering T1D. In our previous study, we showed that Parabacteroides distasonis, a human gut commensal, contains an insB9-23 mimic in its hprt protein (residues 4-18). This mimic (hprt4-18) peptide activates insB9-23-specific T cells, and P. distasonis colonization enhanced diabetes in NOD mice. However, the impact of the P. distasonis colonization on inflammation, gut microbiome, intestinal immune cells, gut permeability, cytokine, and serum metabolome profiles remained unknown. Here, we investigated these effects using specific pathogen-free (SPF) and germ-free (GF) female NOD mice. P. distasonis colonization minimally impacted gut microbiome composition, altering only 28 ASVs. In P. distasonis-colonized mice, there was a reduction in T-helper, T-effector, and B-cell populations in the intraepithelial lymphocytes, indicating a potential decrease in immune activation. Furthermore, P. distasonis colonization did not alter serum metabolome and circulating cytokine profiles (except for a decrease in IL-15) and gut permeability gene expressions. P. distasonis colonization in GF NOD mice induced severe insulitis without affecting gut permeability. Interestingly, mice gavaged with heat-inactivated (HI) P. distasonis did not affect insulitis scores or immune cell composition. These findings support our hypothesis that P. distasonis functions as a gut commensal, exerting no effect on the gut microbiome, metabolome, gut permeability, intestinal immune cell composition, or nonspecific immune activation. Instead, P. distasonis appears to trigger an insB9-23-specific immune response, potentially accelerating T1D onset in NOD mice through molecular mimicry.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873661","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":"PKD and scaffold NHERF1 mediate hypoxia-induced gene expression in 3T3-L1 adipocytes.","authors":"Ying-Yu Wu, Yu-Yao Huang, Juu-Chin Lu","doi":"10.1530/JME-25-0011","DOIUrl":"10.1530/JME-25-0011","url":null,"abstract":"<p><p>Hypoxia has been implicated as a causal factor in mediating adipocyte dysfunction in obesity. Moreover, protein kinase D 1 (PKD1), a serine/threonine protein kinase, has been shown to contribute to diet-induced adiposity. Therefore, we investigated if PKD isoforms mediate hypoxia-induced dysfunction in 3T3-L1 adipocytes. Hypoxia increased phosphorylation of PKD1 at serine 916 (S916), the autophosphorylation site linked to PKD1 activation, indicating hypoxia-induced activation of PKD1 in adipocytes. Inhibition or depletion of PKD isoforms mitigated hypoxia-induced increase in hypoxia-inducible factor 1α (HIF1α), the master transcription factor mediating hypoxia-induced gene expression, confirming that PKDs modulate the hypoxia-induced mechanism in adipocytes. Surprisingly, depletion of PKD1 and PKD2, but not PKD3, attenuated hypoxia-induced HIF1α target gene expression. Unlike PKD3, PKD1 and PKD2 possess a unique PDZ-binding motif at their C-terminus. Indeed, hypoxia upregulated a PDZ-containing scaffold protein Na+/H+ exchanger regulatory factor 1 (NHERF1) and its interaction with PKD1, whereas NHERF1 depletion attenuated hypoxia-induced PKD1 phosphorylation, HIF1α protein accumulation, and gene expression. Mechanistically, hypoxia induced nuclear import of active PKD1, which phosphorylated histone deacetylase 5 (HDAC5) at S498, promoting cytoplasmic localization of HDAC5. HDAC5 deacetylated heat shock protein 70 (HSP70) at lysine 77, which dissociated HSP70 from HIF1α, allowing HSP90 association that stabilized HIF1α. Interestingly, PKD inhibition reversed hypoxia effects on subcellular localization of PKD1/HDAC5, HSP70 acetylation, and HIF1α/HSP90 association. In summary, our findings reveal an NHERF1-PKD1-HDAC5 mechanism modulating hypoxia-induced gene expression in adipocytes.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835393","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":"TNF but not VEGF induces secretion of multiple chemokines and cytokines by uterine artery endothelial cells: potential implications for preeclampsia.","authors":"L Clemente, C Zhou, K Chaiyakul, J H Adams, J Jacobson, J L Austin, D S Boeldt, I M Ong, I M Bird","doi":"10.1530/JME-25-0008","DOIUrl":"10.1530/JME-25-0008","url":null,"abstract":"<p><p>While pregnancy is known to be an inflammatory condition, preeclampsia (PE) is a more extreme state associated with higher cytokines and/or altered growth factors. It is generally assumed these PE-elevated factors come from stimulation of immune cells and/or hypoxic uterine tissue, but several studies have shown that endothelial cells may also be a source. The goal of this study was to determine to what extent TNF, a factor overproduced by uteroplacental tissue in PE pregnancy, may influence uterine artery endothelial cells to contribute to these other PE-specific factors in the maternal circulation. Herein, we use multiple analytical methods to show that uterine artery endothelial cells from pregnant sheep (P-UAEC) on exposure to cytokines can secrete multiple cytokines and chemokines seen in PE women, which may contribute to production of Th17 cells and attraction of these and other cells to the vessel surface. Furthermore, the factors not significantly increased by TNF include those known to be specifically secreted by proinflammatory T cells. This begs the question if endothelium itself is the initial primary orchestrator of chemokine and cytokine imbalance, acting directly and indirectly to promote the symptoms of impaired vasodilation and reduced uteroplacental blood flow. If so, future preventive therapies for PE should be targeted at endothelium as well as immune cells.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784500","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":"Chronic stress-secreted glucocorticoids induce NAFLD-like changes in male rats: oxidative stress/NLRP3 inflammasome signalling.","authors":"Qi Shao, Chuxin Zhang, Jie Mu, Jing Ji, Changxiang Li, Chongyang Ma, Fafeng Cheng","doi":"10.1530/JME-25-0056","DOIUrl":"10.1530/JME-25-0056","url":null,"abstract":"<p><strong>Abstract: </strong>The aim of this study was to investigate the mechanism by which chronic stress (CS) induces non-alcoholic fatty liver disease (NAFLD)-like changes, and the role of oxidative stress and the NLRP3 inflammasome in this mechanism. Transcriptomic data extracted from the Sequence Read Archive (SRA) at the NCBI were employed to identify the molecular targets of CS-induced NAFLD. Fifty 8-week-old healthy male Wistar rats were divided into five groups (n = 10 each) as follows: control, CS, CS + mifepristone (CS + Mif), CS + metyrapone (CS + Met), and corticosterone (Cort). The CS, CS + Mif, and CS + Met groups underwent restraint stress training. Rats in the CS + Mif, CS + Met, and Cort groups were administered mifepristone, metyrapone, and corticosterone for 8 weeks. Data showed that CS induced NAFLD-like liver damage via increased glucocorticoids (GCs). Moreover, CS increased malonaldehyde (MDA) levels and decreased superoxide dismutase (SOD) activity in liver and serum samples, suggesting the occurrence of oxidative stress. Furthermore, CS activated various inflammatory pathways via the NLRP3 inflammasome (NLRP3, ASC, caspase-1), which enhanced cytokine levels (IL-1β, IL-6, TNF-α) in liver tissue. Notably, treatment with metyrapone or mifepristone alleviated liver lesions induced by CS, which implies that the GC signalling pathway may be an important mediator of stress-induced liver inflammation. We conclude that GC mediates the development of oxidative stress and inflammation in the liver, and inhibition of GC signalling may be a new therapeutic strategy in NAFLD.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804329","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":"Dysregulation of hepatic deiodinase type I in metabolically associated steatotic liver disease.","authors":"Nuria Lopez-Alcantara, Alison-Michelle Naujack, Yingfu Chen, Natalie Taege, Cathleen Geißler, Rebecca Oelkrug, Eva K Wirth, Lutz Schomburg, Anita Boelen, Henriette Kirchner, Jens Mittag","doi":"10.1530/JME-25-0096","DOIUrl":"10.1530/JME-25-0096","url":null,"abstract":"<p><p>Hepatic thyroid hormone action plays an important role in preventing the development and progression of metabolic liver diseases, as evidenced by the recent success of the receptor-specific agonist resmetirom. The liver enzyme deiodinase type I (DIO1) is important for controlling the local availability of thyroid hormone and is upregulated in metabolically associated steatotic liver disease (MASLD), which is thought to be a compensatory mechanism to enhance local hormone action. However, it remains unclear whether this increase is maintained in later stages of MASLD and whether an induction of Dio1 can provide beneficial metabolic effects. Studying mouse models with different stages of MASLD, we show here that Dio1 mRNA expression and activity are rapidly induced within 1 week by high-caloric dietary intervention. In later stages, this increase was less pronounced. Surprisingly, altered Dio1 mRNA concentration became progressively less well associated with altered DIO1 enzyme activity, suggesting uncoupling of mRNA and protein biosynthesis. In order to enhance DIO1 activity in MASLD development, a transgenic strategy was applied by using an adeno-associated virus-based liver-specific gene therapy with either the Dio1 or Socs3 gene. In either model, DIO1 activity was increased, but neither thyroid hormone target genes nor metabolic parameters were positively affected in the time frame of the experiment. We conclude that hepatic DIO1 biosynthesis becomes progressively disturbed with disease progression in MASLD by a decoupling of its transcript and protein levels, highlighting the key importance of translational processes controlling DIO1 in hepatocytes, which are likely affected by local inflammatory mechanisms.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753585","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":"Insights into new mechanosensitive behaviors of G protein-coupled receptors.","authors":"Aakanksha J Shetty, Alexei Sirbu, Paolo Annibale","doi":"10.1530/JME-24-0147","DOIUrl":"10.1530/JME-24-0147","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) represent a diverse and vital family of membrane proteins that mediate intracellular signaling in response to extracellular stimuli, playing critical roles in physiology and disease. Traditionally recognized as chemical signal transducers, GPCRs have recently been implicated in mechanotransduction, the process of converting mechanical stimuli into cellular responses. This review explores the emerging role of GPCRs in sensing and responding to mechanical forces, with a particular focus on the cardiovascular system. Cardiovascular homeostasis is heavily influenced by mechanical forces such as shear stress, cyclic stretch, and pressure, which are central to both normal physiology and the pathogenesis of diseases such as hypertension and atherosclerosis. GPCRs, including the angiotensin II type 1 receptor (AT1R) and the β2-adrenergic receptor (β2-AR), have demonstrated the ability to integrate mechanical and chemical signals, potentially through conformational changes and/or modulation of lipid interactions, leading to biased signaling. Recent studies highlight the dual activation mechanisms of GPCRs, with β2-AR now serving as a key example of how mechanical and ligand-dependent pathways contribute to cardiovascular regulation. This review synthesizes current knowledge of GPCR mechanosensitivity, emphasizing its implications for cardiovascular health and disease, and explores advancements in methodologies poised to further unravel the mechanistic intricacies of these receptors.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690571","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":"Evidence for human kisspeptin receptor homo-oligomerisation and its functional relevance.","authors":"Aishwarya P Chakraborty, Vidhi B Rathod, Shobha Sonawane, Shital R Bhanarkar, Bhakti R Pathak, Antara A Banerjee","doi":"10.1530/JME-25-0043","DOIUrl":"10.1530/JME-25-0043","url":null,"abstract":"<p><strong>Abstract: </strong>The signalling of kisspeptin-1 through the kisspeptin-1 receptor (KISS1R) is central to mammalian reproduction. Naturally occurring heterozygous KISS1R mutations and Kiss1r +/- knockout mice are less affected than their homozygous counterparts, suggesting that the mutant receptors possibly form oligomers with the wild-type (WT) KISS1R, rescuing the receptor function to some extent. To test this hypothesis, the heterozygous KISS1R mutations R38P, P46Q, S125L and R198G, reported in the literature in cases of delayed puberty, were characterised. In silico analysis predicted that all four mutations affected the receptor function to varying extents, which was substantiated by in vitro studies. Determination of cell surface receptor expression and kisspeptin-stimulated signalling response was carried out post transient transfection of the receptor constructs in CHO cells. Results revealed that these mutations (homozygous condition) impaired the cell surface receptor expression, as quantified by flow cytometry, with a concomitant attenuation of inositol phosphate production. Co-transfection of the WT KISS1R with equal amounts of the mutant receptors, to mimic the heterozygous condition of the mutation in the patients, restored the receptor function and, with increasing amounts of mutant receptors, resulted in attenuation of receptor function. As a direct proof of receptor oligomerisation, co-expression of epitope-tagged KISS1R constructs was carried out. Co-immunoprecipitation and imaging FRET studies revealed that KISS1R forms homo-oligomers in a constitutive manner and that the transmembrane domain 7 contributed to the oligomerisation interface, as demonstrated by the impairment in oligomerisation upon deletion of this domain. Thus, characterisation of heterozygous KISS1R mutations corroborated the oligomerisation status of the KISS1 receptor and helped in establishing a genotype-phenotype association.</p>","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667792","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}