Endocrine regulations最新文献

{"title":"Beyond canonical GPCR: emerging roles of seven transmembrane proteins in metabolic control - insights from GPR180: A review.","authors":"Lucia Balazova, Matus Antal, Miroslav Balaz","doi":"10.2478/enr-2026-0013","DOIUrl":"10.2478/enr-2026-0013","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) are traditionally defined by their seven-transmembrane (7TM) domain architecture and ability to activate heterotrimeric G proteins. However, accumulating evidence challenges this structure-centric view, revealing a growing class of 7TM proteins that operate through non-canonical mechanisms. GPR180, initially annotated as an orphan GPCR based on predicted 7TM structure, has emerged as a paradigmatic example of this divergence. It lacks demonstrable G protein coupling and instead regulates metabolic function through atypical signalling pathways that influence mitochondrial bioenergetics, lipid handling, and cellular phenotype across multiple metabolic tissues. In adipose tissue, GPR180 controls adipocyte metabolic capacity and thermogenic programming, whereas in the liver, it modulates lipid homeostasis. Importantly, experimental topology analyses reveal inverted membrane orientation, distinguishing GPR180 from <i>bona fide</i> GPCRs despite shared 7TM architecture. Recent structural and functional analyses place GPR180 within the GOST (GOLD-domain 7TM) protein family; here, we propose a metabolically specialized GOST subclass, defined by regulation of mitochondrial bioenergetics and metabolic cell identity rather than classical G protein signalling. Together, these findings argue that GPR180 does not operate as a classical GPCR and highlight the need for functional criteria that extend beyond 7TM architecture when defining receptor identity. More broadly, GPR180 exemplifies how atypical 7TM proteins integrate metabolic state and cellular context to shape signalling output, providing a conceptual framework to systematically identify additional GOST family members with organelle-centred, non-canonical metabolic functions.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"60 1","pages":"122-134"},"PeriodicalIF":0.0,"publicationDate":"2026-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148390193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue-specific steroid hormone-regulated secretion of proteins in <i>Drosophila melanogaster</i> salivary glands - molecular and genetic aspects: A review.","authors":"Robert Farkas, Denisa Benova-Liszekova, Milan Beno","doi":"10.2478/enr-2026-0014","DOIUrl":"10.2478/enr-2026-0014","url":null,"abstract":"<p><p>Larval salivary glands (SGs) of <i>Drosophila melanogaster</i> (further <i>Drosophila</i>) are classical and well-known system, in which steroid hormone ecdysone controlling metamorphosis activates sequence of genes or transcriptional cascade that leads to formation distinct groups of puffs in polytene chromosomes and shortly prior to pupariation to release of unique glue that affix freshly formed puparium to the substrate. Although this system was studied since 1950s and most intensely during 1970s and 1980s, there are still several less known and unappreciated aspects, which deserve special attention. Some functional links between visible puffing and other active genes that do not form puffs are still missing. Production and formation of large secretory granules that are supposed to contain so-called Sgs-material that is secreted upon sturdy increase in ecdysone pulse require plethora of additional and supportive activities of SG cells that were not previously considered to be under direct hormonal control or considered at all. Although some of these physiological processes may appear to be hormone-independent and takes place because all necessary components of particular machinery are already present, there are several other processes that need be coordinated with early, mid or later phase of the ecdysone response and therefore they deserve special attention to fill the gaps. After detailed description of well studies model of Sgs-genes and their hormonal regulation, we tried to integrate this knowledge to a broader context of more advanced and current studies in <i>Drosophila</i> organism or cell lines using whole-genomic approach provided that functional and physiological information is conceptually included. After general introduction to the system, this review is committed to sketch functional and logical connections to processes that are conditionally required to fulfill SG organ-specific function but so far were out of the major research focus.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"60 1","pages":"135-147"},"PeriodicalIF":0.0,"publicationDate":"2026-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148390198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Milder Form of Vici Syndrome Due to Novel Missense Variant in Epg5 Gene Affecting Splicing: A Case Report.","authors":"Martina Skopkova, Katarina Brennerova, Maria Ostrozlikova, Daniela Gasperikova","doi":"10.2478/enr-2026-0015","DOIUrl":"10.2478/enr-2026-0015","url":null,"abstract":"<p><p><b>Objective.</b> Vici syndrome is a rare neurodevelopmental disorder with multisystem involvement, caused by mutations in the <i>EPG5</i> gene encoding a protein involved in autophagy. It includes dysgenesis of the corpus callosum, cataracts, hypopigmentation, cardiomyopathy, and immuno-deficiency. Here we report a case of a 9-year-old boy of Roma ethnicity with a milder form of Vici syndrome and a novel variant in the <i>EPG5</i> gene. <b>Methods.</b> DNA and RNA were extracted from the whole blood. Whole exome sequencing was performed and analysed with an in-house bioinformatics pipeline. A mini-gene assay was performed for <i>EPG5</i> exon 23 with or without the tested variant. <b>Results.</b> The patient was born prematurely and presented with hypotonia, severe hypotrophy and growth retardation, developmental delay, congenital heart defects, mild brain atrophy, and a thin corpus callosum. Whole exome analysis identified a novel variant c.4205G>A, p.(Arg1402Lys) in the <i>EPG5</i> gene, suggesting the diagnosis of Vici syndrome. Further examination of symptoms commonly associated with Vici syndrome confirmed hypopigmented skin areas and immunodeficiency. No seizures, cataracts, or cardiomyopathy were observed. As the variant is located at the last base of exon 23, we sequenced the patient's <i>EPG5</i> mRNA and detected aberrant transcripts in addition to correctly spliced ones. The mini-gene assay confirmed decreased inclusion of the mutated exon compared with the wild-type (40% vs. 72%, respectively). <b>Conclusion.</b> Novel variant <i>EPG5</i>:c.4205G>A, p.(Arg1402Lys) causes aberrant splicing only in a small proportion of transcripts; therefore, the milder presentation of Vici syndrome in our patient is probably due to the residual presence of EPG5 protein.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"60 1","pages":"148-158"},"PeriodicalIF":0.0,"publicationDate":"2026-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148390131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocannabinoid signalling in the regulation of hypothalamic-pituitary neuroendocrine circuits: A review.","authors":"Anabela Nagyova, Natasa Hlavacova","doi":"10.2478/enr-2026-0011","DOIUrl":"10.2478/enr-2026-0011","url":null,"abstract":"<p><p>The endocannabinoid system (ECS), comprising cannabinoid receptors, endogenous lipid ligands, and enzymes that regulate their synthesis and degradation, has emerged as an important modulator of neuroendocrine regulation. This review summarises current evidence on the role of endocannabinoid signalling in hypothalamic-pituitary neuroendocrine circuits, with particular focus on the hypothalamic-pituitary-adrenocortical, gonadal, thyroid, and somatotropic axes, as well as prolactin and posterior pituitary hormones regulation. Available data indicate that endocannabinoid signalling predominantly influences neuroendocrine function by modulating synaptic transmission within hypothalamic circuits. Acting mainly as retrograde messengers at presynaptic CB1 receptors, endocannabinoids regulate excitatory and inhibitory inputs to neurosecretory neurons and thus shape endocrine output in a context-dependent manner. Among the systems discussed, the hypothalamic-pituitary-adrenocortical axis is the best characterised, with relatively well-defined links between glucocorticoid feedback and rapid endocannabinoid-mediated suppression of synaptic input to corticotropin-releasing hormone neurons. In other neuroendocrine systems, evidence supports a predominantly modulatory, often inhibitory, role for endocannabinoid signalling, although the underlying cellular processes remain less well-defined and are largely based on preclinical studies. Interactions with glucocorticoids, gonadal steroids and neuropeptidergic pathways further underscore the integrative nature of ECS signalling. Overall, the ECS should be viewed not as a primary endocrine driver, but as a dynamic regulatory network that fine-tunes the translation of neural activity into hormonal responses.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"60 1","pages":"98-110"},"PeriodicalIF":0.0,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148344400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current perspectives on the pathogenesis of multiple sclerosis: A minireview.","authors":"Zofia Radikova, Miroslav Tibensky, Lucia Mosna, Adela Penesova, Andrea Havranova, Miroslav Vlcek, Richard Imrich","doi":"10.2478/enr-2026-0009","DOIUrl":"10.2478/enr-2026-0009","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the central nervous system characterized by inflammation, reactive gliosis, and progressive neuroaxonal damage resulting in heterogeneous clinical and histopathological manifestations. As MS often leads to disability at a young age, it represents a substantial socio-economic burden in developed countries. The etiopathogenesis of MS is multifactorial and incompletely understood, involving genetic, immunologic, and environmental factors. Recent research highlights immune responses to Epstein-Barr virus, blood-brain barrier disruption, microbiome-gut-brain axis alterations, oxidative damage, and mitochondrial dysfunction. Studying patients with newly diagnosed MS without significant comorbidities provides insight into early disease mechanisms before disability development or long-term treatment effects. This mini-review focuses on early vascular and metabolic alterations that may contribute to MS, including lipoprotein subfractions as markers of incipient atherosclerosis, endothelial dysfunction as an initiating vascular event, and autonomic nervous system imbalance during disease progression. It also addresses insulin sensitivity as a key metabolic factor alongside chronic inflammation and oxidative damage as interconnected mechanisms driving tissue injury. Metabolic changes reflecting neuronal impairment, mitochondrial dysfunction, and astroglial activation are detectable in both lesional and normal-appearing white matter in early stages. Reduced antioxidant capacity supports a role of oxidative damage in MS pathogenesis. Accelerated vascular aging, independent of traditional cardiovascular risk factors, may progress from endothelial dysfunction to structural atherosclerotic changes. Subtle alterations in lipoprotein profiles further suggest an increased risk of atherosclerosis, potentially influenced by inflammatory activity and oxidative damage, with possible sex-specific differences. Autonomic dysfunction appears to develop secondary to disease progression rather than as a primary driver of pathogenesis.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"60 1","pages":"72-85"},"PeriodicalIF":0.0,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148344375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early life adversity influences brain development through neuroendocrine, immune, and microbiota-related mechanisms: A review.","authors":"Peter Vargovic, Jana Osacka, Lubica Horvathova, Andrej Tillinger, Denisa Mihalj, Barbora Bugar Bodorova, Lila Dziewiczova, Tomas Havranek, Zuzana Bacova, Jan Bakos","doi":"10.2478/enr-2026-0010","DOIUrl":"10.2478/enr-2026-0010","url":null,"abstract":"<p><p>The early life experiences have an important impact on the development of the brain and behavior and early life adversities (ELA) may affect several biological systems including the hypothalamic-pituitary-adrenal (HPA) axis, neurotransmitter and immune signaling systems, and microbiota composition. Dysregulation of these systems may result in an altered stress reactivity in both early life and the adulthood periods leading to maladaptive responses to the environmental stimuli. The activation of certain neuropeptides, including oxytocin, stimulation of the HPA axis, and increased glucocorticoid levels, may also play an important role in the early adaptive processes. In terms of brain maturation, ELA can directly or indirectly elicit structural changes in neurite growth, neurogenesis, neuronal connectivities, and signaling processes, which may contribute to the production of the long-term behavioral changes associated with an increased risk of the neuropsychiatric disorders' development in later periods of the life. In this review, we summarize the effect of ELA on the HPA axis function, stress-related hormonal balance, immune responses, and the gut microbiome indicating how these changes may affect the brain function and behavior in the early stages of the life and adulthood. We also provide insight into animal studies revealing the responses of corticotropin-releasing hormone, urocortins, and corticosterone in various neural circuits in response to ELA evoked by maternal separation and limited bedding paradigms.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"60 1","pages":"86-97"},"PeriodicalIF":0.0,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148344385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and predictors of poor glycemic control in patients with type 2 diabetes mellitus attending Alexandria Main University Hospital.","authors":"Heba S Kassab, Fathy Z Alsewy, Sherif M Abdelaziz, Reem M Fathalla","doi":"10.2478/enr-2026-0002","DOIUrl":"10.2478/enr-2026-0002","url":null,"abstract":"<p><p><b>Objective.</b> Despite the advances in diabetes management, there is still a high prevalence of poor glycemic control worldwide. This study aimed to determine the prevalence and predictors of poor glycemic control among patients with type 2 diabetes mellitus (T2DM) attending the outpatient clinic at Alexandria Main University Hospital (AMUH) Egypt. <b>Methods.</b> This cross-sectional study was conducted on 290 patients with T2DM. Data were collected on sociodemographic factors, medical history, comorbidities, lifestyle behaviors, medication adherence, and biochemical measures. Statistical analyses including correlation and regression models were used to explore the relationships between various factors and glycemic control. <b>Results.</b> The study revealed that 82.8% of participants had uncontrolled diabetes. Poor glycemic control was significantly associated with older age, lower education, rural residence, unemployment, and lower income. Additionally, patients with uncontrolled diabetes had higher rates of hypertension, dyslipidemia, ischemic heart disease, and diabetic peripheral neuropathy. Better physical activity and dietary adherence were linked to improved glycemic control, while medication adherence was significantly lower in the uncontrolled group. Among the significant predictors, physical activity (ORs=116.6-575.8) was the strongest predictor of improved diabetes control. Moreover, medication adherence (OR=4.098) and higher education (OR=8.354) were strongly associated with better diabetes control. <b>Conclusions.</b> Socioeconomic factors, lifestyle behaviors, and medication adherence are key predictors of glycemic control in T2DM patients. Physical activity, medication adherence, and higher education were the strongest predictors of better glycemic control. Addressing these factors through targeted interventions, particularly in rural areas, is crucial for improving diabetes management and reducing the related complications.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"60 1","pages":"12-19"},"PeriodicalIF":0.0,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One genotype with a myriad of phenotypes: A family with multiple endocrine neoplasia.","authors":"Oumeyma Trimeche, Fatma Mnif, Fatma Abdelhedi, Kaouther El Arbi, Yosra Lajmi, Nadia Charfi, Mouna Mnif, Faten Hadj Kacem, Dhouha Ben Salah, Khouloud Boujelbene, Mohammed Abid, Mouna Elleuch, Nebila Rekik","doi":"10.2478/enr-2026-0004","DOIUrl":"10.2478/enr-2026-0004","url":null,"abstract":"<p><p><b>Objective.</b> Multiple endocrine neoplasia type 1 (MEN1) is a very rare genetic disorder characterized by an autosomal dominant inheritance. We aim through this case series to delineate the wide spectrum of its clinical features. <b>Methods.</b> In the present study, we report the clinical and genetic findings of four siblings affected by this disorder. DNA was extracted from patients' blood leukocytes using a phenol-chloroform method and assessed for purity with a NanoDrop spectrophotometer. Ten exons of the <i>MEN1</i> gene were amplified by PCR, verified by gel electrophoresis, and sequenced using Big Dye Terminator chemistry followed by capillary electrophoresis. The sequences were than analyzed with CHROMAS and compared to reference sequences. As for the variant, interpretation and pathogenicity were assessed using Ensembl, ClinVar, dbSNP, gnomAD, Alamut Visual, and VARSOME. <b>Results.</b> We highlight the wide range of phenotypes encompassing primary hyperparathyroidism, macroprolactinoma, lipomas, papillary thyroid carcinoma, ectopic thyroid, multinodular goiter, and bilateral adrenal nodules observed in this family contrasting with the same pathogenic frameshift mutation. We also pinpoint to a second mutation detected in two of the siblings while discussing its pathogenicity. Finally, we provide an overview of the clinical manifestations of MEN1 and its genetic background. <b>Conclusion.</b> This research sets the stage to further investigate the molecular mechanisms underlying the novel nonsense mutation. Additionally, it incites other research to explore the frequency of this mutation in other populations and finally to conduct functional studies.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"60 1","pages":"29-36"},"PeriodicalIF":0.0,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of the risk factors impact on the life quality of patients with arterial hypertension.","authors":"Svitlana Pidruchna, Nadiya Yarema, Iryna Kuzmak, Olena Prokopovych, Volodymyr Shmanko, Oleh Shmanko, Petro Lykhatskyi, Oksana Ostrivka, Alla Mudra, Lylya Palytsya, Nataliya Letniak, Tetyana Yaroshenko, Oksana Pohorielova, Olena Chernyshenko","doi":"10.2478/enr-2026-0007","DOIUrl":"10.2478/enr-2026-0007","url":null,"abstract":"<p><p><b>Objective.</b> Recently, multicomponent quality-of-life indicators have become increasingly important in monitoring the health status of patients with hypertension and evaluating the effectiveness of treatment. Improving patient quality of life is considered one of the key objectives of the medical intervention. <b>Methods.</b> To assess the quality of life of patients with, we used the standardized SF-36 (Short Form-36 Health Survey) questionnaire, which allows to explicitly examine the respondent physical and psycho-emotional status. <b>Results.</b> We analyzed the association between polymorphisms of endothelial nitric oxide (NO) synthase (eNOS) (NOS3, T786C) and angiotensin II receptor type 1 (AGTR1, A1166C) genes and quality of life. Patients with polymorphisms associated with lower intravascular pressure had lower baseline QoL scores, particularly on the \"physical functioning\" and \"general health\" scales (p<0.05). Patients with heterozygous or homozygous \"unfavorable\" genotypes (AGTR1_CC, NOS3_CC) have significantly lower total indicators of both physical and psycho-emotional health compared to patients with \"better\" genotypes (AA, TT) and the control group. <b>Conclusion.</b> Patients with polymorphisms that cause reduced bioavailability of NO or excessive activation of AGRT1 show a significant deterioration in quality of life on all key SF-36 scales. This indicates the significant role of genetic factors in shaping the subjective perception of health in patients with arterial hypertension.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"60 1","pages":"55-60"},"PeriodicalIF":0.0,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of ERN1 suppresses the expression of phosphoenolpyruvate carboxykinase 2 in U87MG glioblastoma cells and increases its sensitivity to glucose and glutamine deprivation.","authors":"Yuliia M Viletska, Oleksandr H Minchenko, Olena O Khita, Myroslava Y Sliusar, Oleh V Halkin, Halyna E Kozynkevych, Dmytro O Minchenko","doi":"10.2478/enr-2026-0008","DOIUrl":"10.2478/enr-2026-0008","url":null,"abstract":"<p><p><b>Objective.</b> Phosphoenolpyruvate carboxykinase (PCK) catalyzes the conversion of oxaloacetate to phosphoenolpyruvate and regulates pyruvate metabolism and gluconeogenesis in response to glucocorticoid and insulin stimuli. Mitochondrial isoform of this enzyme (PCK2) is overexpressed in glioblastoma cells and participates in metabolic reprogramming and cell proliferation. This study aims to examine the impact of ERN1 (endoplasmic reticulum to nucleus signaling 1) inhibition on PCK2 expression and sensitivity to glucose and glutamine deprivation to determine the role of ERN1 signaling in the regulating its expression in glioblastoma cells. <b>Methods.</b> The glioblastoma cell line U87MG and two genetically modified variants of these cells were used. These were glioblastoma cell sublines with suppressed endoribonuclease and protein kinase activities of ERN1 (dnERN1) or only ERN1 endoribonuclease (dnrERN1), and control cells transfected with an empty vector. The suppression of ERN1 function by silencing of ERN1 and XBP1 mRNAs was also used. Hypoxia was generated using the HIF1A prolyl hydroxylase inhibitor dimethyloxalylglycine. For glucose and glutamine deprivation, DMEM medium without glucose or glutamine was used. The expression level of the PCK2 mRNA was analyzed by real-time qPCR and normalized to the beta-actin mRNA. <b>Results.</b> It has been demonstrated that PCK2 mRNA expression is significantly decreased in dnERN1 glioblastoma cells. Similar suppression of this mRNA expression was also observed in cells with only the endoribonuclease activity of ERN1 inhibited, indicating that this enzymatic activity is involved in the regulation of PCK2 expression. The silencing of ERN1 and XBP1 mRNAs also induced similar changes in PCK2 mRNA expression, possibly mediated by XBP1s. The expression of PCK2 was enhanced under glutamine deprivation in control glioblastoma cells, but inhibition of ERN1 activity strongly increased this effect. Upregulated PCK2 expression was also observed in control glioblastoma cells under glucose deprivation. However, the inhibition of ERN1 activity strongly increased the sensitivity of this gene expression to glucose deprivation. Furthermore, PCK2 mRNA expression was resistant to hypoxic conditions in cells with native ERN1. At the same time, in glioblastoma cells with inhibited ERN1 activity, a strong induction of PCK2 expression was observed. <b>Conclusion.</b> The results of this study demonstrated that ERN1 inhibition reduces PCK2 mRNA expression through the ERN1 endoribonuclease activity. This mRNA expression is upregulated under glutamine and glucose deprivation. Moreover, ERN1 inhibition strongly enhanced the sensitivity of PCK2 mRNA expression to glucose and glutamine deprivation as well as to hypoxia.</p>","PeriodicalId":11650,"journal":{"name":"Endocrine regulations","volume":"60 1","pages":"61-71"},"PeriodicalIF":0.0,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}