Journal of molecular endocrinology最新文献_第2页

A framework to map cAMP signalling nanodomains: phosphodiesterase-centred phosphoproteome-interactome networks (pPINs) in cardiac myocytes. 绘制cAMP信号纳米结构域的框架：心肌细胞中以磷酸二酯酶为中心的磷酸蛋白质组相互作用组网络（pPINs）。

IF 3.1 4区医学

Journal of molecular endocrinology Pub Date : 2026-08-01 DOI: 10.1530/JME-26-0089

Duangnapa Kovanich, Manuela Zaccolo

{"title":"A framework to map cAMP signalling nanodomains: phosphodiesterase-centred phosphoproteome-interactome networks (pPINs) in cardiac myocytes.","authors":"Duangnapa Kovanich, Manuela Zaccolo","doi":"10.1530/JME-26-0089","DOIUrl":"10.1530/JME-26-0089","url":null,"abstract":"Intracellular signalling is commonly represented as linear pathways that connect receptors to downstream effectors. While such models have been instrumental in defining signalling cascades, they fail to capture the spatial organisation that underlies signalling specificity in living cells. The cyclic adenosine monophosphate (cAMP) pathway provides a well-established example of this principle, where signalling is compartmentalised into nanometre-scale domains that generate highly localised and functionally distinct responses. However, a comprehensive framework for defining the molecular composition, spatial organisation and functional outputs of these signalling domains and how they adapt to perturbations remains lacking. Here, we discuss how integrative proteomics approaches can be used to reconstruct the subcellular cartography of compartmentalised signalling networks. By combining isoform-specific interactomics, quantitative phosphoproteomics, network analysis and spatial annotation, individual signalling platforms can be mapped within their native intracellular context. We introduce phosphoproteome-interactome networks (pPINs), a systems-level framework that integrates molecular interactions, subcellular localisation and phosphorylation responses to define phosphodiesterase (PDE)-centred signalling platforms and their associated signalling outputs. Using PDE3A isoforms as an example, we illustrate how pPINs uncover multiple spatially distinct cAMP signalling nanodomains in cardiac myocytes and reveal previously unrecognised biology, including a nuclear PDE3A2/SMAD4/HDAC-1 platform that locally constrains PKA activity and suppresses prohypertrophic gene expression. More broadly, pPINs provide a conceptual and computational framework for resolving the spatial architecture of intracellular signalling networks and establish a foundation for precision therapeutic strategies targeting discrete signalling microenvironments.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886934","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}

引用次数: 0

An analysis of intestinal morphology and incretin-producing cells after sleeve gastrectomy in male mice. 雄性小鼠袖式胃切除术后肠道形态及肠促胰岛素产生细胞的分析。

IF 3.1 4区医学

Journal of molecular endocrinology Pub Date : 2026-08-01 DOI: 10.1530/JME-26-0016

Naoki Wada, Norio Harada, Eri Ikeguchi-Ogura, Sakura Kiyobayashi, Tomonobu Hatoko, Yohei Seno, Takashi Kurihara, Yosuke Kaido, Kana Yamamoto, Takuma Yasuda, Yoshitaka Hayashi, Nobuya Inagaki, Daisuke Yabe

{"title":"An analysis of intestinal morphology and incretin-producing cells after sleeve gastrectomy in male mice.","authors":"Naoki Wada, Norio Harada, Eri Ikeguchi-Ogura, Sakura Kiyobayashi, Tomonobu Hatoko, Yohei Seno, Takashi Kurihara, Yosuke Kaido, Kana Yamamoto, Takuma Yasuda, Yoshitaka Hayashi, Nobuya Inagaki, Daisuke Yabe","doi":"10.1530/JME-26-0016","DOIUrl":"10.1530/JME-26-0016","url":null,"abstract":"Sleeve gastrectomy (SG) is an effective treatment for obesity. SG increases glucagon-like peptide-1 (GLP-1) secretion; however, its effect on glucose-dependent insulinotropic polypeptide (GIP) remains unclear. Previous studies investigating changes in intestinal morphology, the number of GLP-1-producing cells (enteroendocrine L cells), and the number of GIP-producing cells (enteroendocrine K cells) after SG have been based on two-dimensional histological evaluations. In this study, we performed three-dimensional (3D) evaluations using a tissue-clearing method to precisely elucidate the intestinal morphology and incretin-producing cell number after SG in various tissue-specific reporter mouse strains. Insulin and GLP-1 secretion were significantly higher in SG mice compared with sham-operated mice, whereas GIP secretion did not differ between these two mouse groups. The villus length and width of the villus major axis in the duodenum were significantly shorter in SG mice. After SG, the number of villus L cells became significantly higher in the ileum, but did not change in the colon. After SG, the number of villus K cells became significantly lower in the duodenum. This is the first study to provide a 3D morphological evaluation of the entire intestine after SG. Intestinal morphology and the number and localization of incretin-producing cells within villi and crypts can be comprehensively quantified.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794467","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}

引用次数: 0

Chloride-permeable channels in white adipocytes: their role in adipogenesis and membrane potential. 白色脂肪细胞中的氯离子渗透通道：它们在脂肪形成和膜电位中的作用。

IF 3.1 4区医学

Journal of molecular endocrinology Pub Date : 2026-08-01 DOI: 10.1530/JME-25-0111

Yan Meng, Paul A Smith

{"title":"Chloride-permeable channels in white adipocytes: their role in adipogenesis and membrane potential.","authors":"Yan Meng, Paul A Smith","doi":"10.1530/JME-25-0111","DOIUrl":"10.1530/JME-25-0111","url":null,"abstract":"Ion fluxes, regulated by membrane potential (Vm), are vital to white fat adipocyte (WFA) function and adipogenesis. These processes present a novel target to intervene in obesity. To explore this possibility, we applied transcriptomics, immunohistochemistry, electrophysiology, and adipogenesis assays alongside siRNA and pharmacological tools to identify the chloride-permeable channel(s) that determine the Vm of WFA and to test whether those channels - specifically SWELL1 (Lrrc8 family), TTYH2/3, and EAAT1 - regulate adipocyte differentiation and adipogenesis. RNA sequencing and qPCR confirmed the existence of Lrrc8a, Lrrc8b, Lrrc8c, Lrrc8d, Ttyh2, Ttyh3, Slc1a1, and Ano1 transcripts across different primary fat depots of rats and mice, as well as a subset within 3T3-L1 adipocytes. The corresponding protein products, SWELL1 (Lrrc8x), TTYH2/3 (Ttyh2/3), and EAAT1 (Slc1a1), were found in both the plasma membrane and cytoplasm of primary and differentiated 3T3-L1 adipocytes, whereas TMEM16A protein was only in primary adipocytes and undifferentiated 3T3-L1 pre-adipocytes. Functional studies showed that although siRNA knockdown or pharmacological blockade of SWELL1, TTYH2/3, or EAAT1 proteins did not affect adipocyte Vm or electrophysiological characteristics, SWELL1 and TTYH2/3 knockdown significantly suppressed adipocyte differentiation and adipogenesis. Together, these findings reveal a role for SWELL1, TTYH2/3, and EAAT1 in adipogenesis and highlight their potential as targets for therapeutic strategies in obesity management. Although the precise chloride permeability responsible for adipocyte Vm remains to be defined, this work advances our understanding of adipocyte biology.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679015","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}

引用次数: 0

Pancreatic β-cell aging in physiology and diabetes: emerging roles of m6A mRNA methylation. 胰腺β细胞在生理和糖尿病中的衰老：m6A mRNA甲基化的新作用。

IF 3.1 4区医学

Journal of molecular endocrinology Pub Date : 2026-07-01 DOI: 10.1530/JME-25-0159

Lenee Shrestha, Dario F De Jesus

{"title":"Pancreatic β-cell aging in physiology and diabetes: emerging roles of m6A mRNA methylation.","authors":"Lenee Shrestha, Dario F De Jesus","doi":"10.1530/JME-25-0159","DOIUrl":"10.1530/JME-25-0159","url":null,"abstract":"Pancreatic β-cells are essential for glucose homeostasis and are particularly vulnerable to age-related stress. Aging is a fundamental biological process characterized by the progressive functional decline of tissues and organs and defined by several interconnected hallmarks. In type 1 and type 2 diabetes, aging is accelerated - manifesting as DNA damage response, endoplasmic reticulum stress, and mitochondrial dysfunction, collectively driving β-cell dysfunction and senescence. N6-methyladenosine (m6A) is the most prevalent internal messenger RNA (mRNA) modification in eukaryotes. Emerging evidence demonstrates that m6A levels change with age in a tissue-specific manner, contributing to cellular dysfunction and age-related disease. In pancreatic β-cells, m6A hypomethylation compromises identity, survival, and function through mechanisms that include the IGF1 and insulin signaling pathways. Understanding how m6A methylation is regulated in aged β-cells may uncover new therapeutic strategies aimed at preserving β-cell functional mass and promoting healthy aging. This review focuses on pancreatic β-cell aging in physiological and diabetic conditions and examines the emerging role of m6A methylation in aging and diabetes progression.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218073","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}

引用次数: 0

Novel gain-of-function CLCN2 germline mutation associated with nonclassical lateralizing primary aldosteronism. 与非经典偏侧原发性醛固酮增多症相关的新型功能获得性CLCN2种系突变。

IF 3.1 4区医学

Journal of molecular endocrinology Pub Date : 2026-07-01 DOI: 10.1530/JME-25-0176

Ssu-Ju Fu, Kang-Yung Peng, Ya-Hui Hu, Yen-Yu Lin, Chia-Ying You, Pei-Chen Tsai, An-Ting Cheng, Vin-Cent Wu, Meng-Chun Hu, Chih-Yung Tang

{"title":"Novel gain-of-function CLCN2 germline mutation associated with nonclassical lateralizing primary aldosteronism.","authors":"Ssu-Ju Fu, Kang-Yung Peng, Ya-Hui Hu, Yen-Yu Lin, Chia-Ying You, Pei-Chen Tsai, An-Ting Cheng, Vin-Cent Wu, Meng-Chun Hu, Chih-Yung Tang","doi":"10.1530/JME-25-0176","DOIUrl":"10.1530/JME-25-0176","url":null,"abstract":"Primary aldosteronism (PA) is commonly caused by somatic and germline mutations in various genes. Patients with unilateral PA may display classical or nonclassical histopathologic features in adrenal tumors. Somatic and germline mutations are linked to classical unilateral and familial PA, respectively. In this study, we aim to search for novel gene mutations causing nonclassical lateralizing PA. Surgically resected adrenal tumor tissues from patients enrolled in a PA cohort were subjected to histopathological evaluation. Genetic analyses were performed for genomic DNA isolated from peripheral blood leukocytes and CYP11B2 immunohistochemistry-guided macrodissected adrenal tissues to identify novel variants. A PA patient with a 1.8 cm mass in the right adrenal gland underwent laparoscopic right adrenalectomy and achieved complete biochemical success at 12 months, but partial clinical improvement. Post-adrenalectomy tissues displayed the nonclassical histopathologic feature with multiple aldosterone-producing micronodules (mAPMs), but no solitary aldosterone-producing adenoma. Genetic analyses identified a heterozygous CLCN2 germline variant, c.1087C>T (p.R363C), that was likely pathogenic based on bioinformatic evaluations. In vitro biochemical, electrophysiological, and hormone assays revealed that the human ClC-2 R363C Cl- channel displayed significant gain-of-function phenotypes, including enhanced protein stability and cell surface expression, higher channel open probability at physiological membrane potentials, and increased aldosterone production in human adrenocortical cells. The dominant gain-of-function effect of ClC-2 R363C was also observed when we co-expressed the variant with its wild-type counterpart. Altogether, we report the first association of gain-of-function CLCN2 germline mutation with nonclassical mAPMs, providing new insights into the pathogenic mechanisms of PA.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430641","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}

引用次数: 0

CRISPR activation of DLX5 drives neural progenitors to the GnRH cell fate. CRISPR激活DLX5驱动神经祖细胞走向GnRH细胞命运。

IF 3.1 4区医学

Journal of molecular endocrinology Pub Date : 2026-07-01 DOI: 10.1530/JME-26-0040

Shrinidhi Madhusudan, Nazli Eskici, Celia Gomez-Sanchez, Kristiina Pulli, Kirsi Vaaralahti, Venkatram Yellapragada, James R W Conway, Yafei Wang, Taneli Raivio

{"title":"CRISPR activation of DLX5 drives neural progenitors to the GnRH cell fate.","authors":"Shrinidhi Madhusudan, Nazli Eskici, Celia Gomez-Sanchez, Kristiina Pulli, Kirsi Vaaralahti, Venkatram Yellapragada, James R W Conway, Yafei Wang, Taneli Raivio","doi":"10.1530/JME-26-0040","DOIUrl":"10.1530/JME-26-0040","url":null,"abstract":"Gonadotropin-releasing hormone (GnRH) neurons regulate the hypothalamic-pituitary-gonadal (HPG) axis and are required for puberty onset and reproductive competence. However, the transcriptional regulators governing GnRH neuron specification and migration remain poorly defined. The homeodomain transcription factor DLX5 is expressed in fetal human GnRH neurons, its expression precedes that of GNRH1 in human pluripotent stem cell (hPSC)-derived GnRH neurons, and in mice, it serves as a guidance cue for GnRH neuron migration. We hypothesized that DLX5 may act as an upstream regulator of human GnRH neuron fate specification and migratory capacity. Using CRISPR activation, we upregulated DLX5 during FGF8b-directed differentiation of hPSCs to GnRH neurons via dual SMAD inhibition and Notch inhibition, as previously described. DLX5 activation increased neural progenitor motility (P < 0.001), upregulated FGF8 (P < 0.05), and induced GABAergic markers, including GAD1 and GAD2. Notably, DLX5 activation induced GNRH1 in the absence of exogenous FGF8b (P < 0.05), suggesting that in GnRH neurons, DLX5 regulates FGF8. When combined with exogenous FGF8b, DLX5 activation produced distinct neuronal patterning accompanied by upregulation of extracellular matrix genes, such as SPARC, which has been implicated in neurite outgrowth. Collectively, these data indicate that activation of DLX5 promotes GnRH neurogenesis from hPSCs, by driving GABAergic fate, inducing FGF8, and remodeling the extracellular matrix.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13400967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447439","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}

引用次数: 0

ROS-driven mitochondrial and mtDNA release as a novel pathway of metabolic injury in diabetes. ros驱动的线粒体和mtDNA释放是糖尿病代谢损伤的新途径。

IF 3.1 4区医学

Journal of molecular endocrinology Pub Date : 2026-07-01 DOI: 10.1530/JME-25-0203

Dandan Chen, Yuxin Jia, Xiaohong Duan, Jianhua Huang, Xiaohong Deng

{"title":"ROS-driven mitochondrial and mtDNA release as a novel pathway of metabolic injury in diabetes.","authors":"Dandan Chen, Yuxin Jia, Xiaohong Duan, Jianhua Huang, Xiaohong Deng","doi":"10.1530/JME-25-0203","DOIUrl":"10.1530/JME-25-0203","url":null,"abstract":"Mitochondrial dysfunction driven by chronic hyperglycemia is a hallmark of diabetes, yet how this metabolic stress communicates pathological signals beyond individual cells remains poorly understood. In this study, we identified a novel mechanism linking chronic hyperglycemia to systemic metabolic impairment through ROS-mediated extracellular release of structurally intact mitochondria and mitochondrial DNA (mtDNA). In HepG2 cells exposed to high glucose (HG), extracellular release of structurally intact mitochondria was visualized by co-staining of mitochondria and the plasma membrane, together with electron microscopy. Mitochondria-enriched fractions isolated from culture supernatants were further quantified using flow cytometry and qPCR. Cell-free mtDNA (cf-mtDNA) was visualized with co-staining of mitochondria and double-stranded DNA, isolated through differential centrifugation and ultrafiltration, and quantified by qPCR. We demonstrate that HG stimulates the release of exosome-enclosed mtDNA and fragmented cf-mtDNA. Concurrently, HG induces mitochondrial dysfunction and markedly increases mitochondrial ROS (mtROS). Treatment with MitoTEMPO, a mitochondria-targeted ROS scavenger, significantly reduced HG-induced extracellular release of mitochondria and mtDNA, supporting the ROS dependence of this process. In diabetic mice, we detected elevated circulating mtDNA copy number and pronounced mitochondrial dysfunction in liver and muscle, including reduced ATP production, mitochondrial swelling, cristae disruption, and elevated MDA levels. Resting metabolic rate was markedly decreased, indicating impaired systemic respiratory metabolism. Serum analyses revealed increased 8-OHdG, pyruvic acid, GDF-15, and FGF-21, along with reduced FT3, reflecting severe oxidative stress and mtDNA damage. These findings uncover a novel mechanism in which hyperglycemia-induced ROS drive mitochondrial extrusion, potentially linking metabolic stress to systemic metabolic deterioration.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471377","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}

引用次数: 0

A computational systems biology view on the role of the menstrual cycle in endocrine health and disease. 月经周期在内分泌健康和疾病中的作用的计算系统生物学观点。

IF 3.1 4区医学

Journal of molecular endocrinology Pub Date : 2026-07-01 DOI: 10.1530/JME-25-0211

Susanna Röblitz

{"title":"A computational systems biology view on the role of the menstrual cycle in endocrine health and disease.","authors":"Susanna Röblitz","doi":"10.1530/JME-25-0211","DOIUrl":"10.1530/JME-25-0211","url":null,"abstract":"In the era of personalized and precision medicine, sex is an important biological variable that needs to be taken into account in biomedical research. However, the role of the menstrual cycle has long been neglected because it requires clinical studies that are large, time-consuming, and expensive. A computational systems biology approach is a fundamentally different but powerful framework that explains how architectural features of the hormonal system, including feedback loops and cross-talk mechanisms, give rise to emergent behavior on the system level. Nevertheless, systems biology models that are centered around the menstrual cycle are still scarce. A major challenge both in medical research and from a modeling point of view is the large intra- and inter-individual variability in cycle length. In fact, the hypothalamic-pituitary-ovarian (HPO) axis, which is responsible for the regulation of the menstrual cycle, interacts with many of the other hormonal systems that are involved in, for example, the regulation of stress, energy balance, and glucose homeostasis. These interactions and their age-related changes need to be considered when exploring normal and pathological conditions since many endocrine diseases go along with disruptions in multiple hormonal axes. This paper focuses on the HPO axis and its interactions with the hypothalamic-pituitary-adrenal axis and glucose-insulin metabolism in both health and disease. It briefly summarizes the biomedical knowledge about the individual sub-systems and their cross-talk mechanisms and provides an overview of mathematical modeling approaches and opportunities in this field.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148264885","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}

引用次数: 0

Neuroendocrine regulation of female fertility: the role of CNS-derived hormones. 神经内分泌对女性生育的调节：中枢神经系统衍生激素的作用。

IF 3.1 4区医学

Journal of molecular endocrinology Pub Date : 2026-07-01 DOI: 10.1530/JME-25-0049

Amirreza Shakoeizadeh, Erfan Shahabinejad, Mahdi Heydari, Amirmohammad Shahidzadeh, Soheila Pourmasumi

{"title":"Neuroendocrine regulation of female fertility: the role of CNS-derived hormones.","authors":"Amirreza Shakoeizadeh, Erfan Shahabinejad, Mahdi Heydari, Amirmohammad Shahidzadeh, Soheila Pourmasumi","doi":"10.1530/JME-25-0049","DOIUrl":"10.1530/JME-25-0049","url":null,"abstract":"Infertility is an increasing concern for many women and can affect both physical and emotional well-being. The central nervous system (CNS) - particularly the hypothalamus, pituitary gland, and pineal gland - plays a crucial role in female reproductive health. We conducted a narrative review of relevant studies published between 2015 and 2025, sourcing data from PubMed and Scopus. Our goal was to investigate how dysregulation of hormones from the hypothalamus, pituitary gland, and pineal gland contributes to fertility-related disorders, such as impairments in ovulation, oocyte quality, and embryo development. Both human and significant animal studies were considered to better understand how CNS hormones affect fertility. The findings emphasize the roles of key hormones, including gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), melatonin, adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), and vasopressin (ADH). The proper timing and balance of these hormones are vital. For instance, GnRH pulses regulate the release of LH and FSH, which are essential for ovulation and follicle development. Melatonin supports oocyte health and helps maintain the menstrual cycle, while ACTH and TSH are also involved in reproductive function. Vasopressin affects uterine activity and hormone production. Understanding these hormonal interactions may lead to better diagnostic tools and more effective treatment strategies for conditions such as polycystic ovary syndrome (PCOS) and other fertility-related disorders. Unlike previous studies, this research provides a comprehensive investigation of how CNS-mediated hormonal regulation influences female reproductive outcomes, examining the roles of all involved hormones.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218058","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}

引用次数: 0

OGT accelerates diabetic retinopathy via O-GlcNAcylation of BAP1. OGT通过o - glcn酰化BAP1加速糖尿病视网膜病变。

IF 3.1 4区医学

Journal of molecular endocrinology Pub Date : 2026-06-09 Print Date: 2026-05-01 DOI: 10.1530/JME-25-0065

Bairong Wang, Junteng Yao, Yuren Zhang, Meirong Li, Jinting Xu, Yinan Chen, Yiping Zhang, Qiaolan Liu, Xiaoting Li

{"title":"OGT accelerates diabetic retinopathy via O-GlcNAcylation of BAP1.","authors":"Bairong Wang, Junteng Yao, Yuren Zhang, Meirong Li, Jinting Xu, Yinan Chen, Yiping Zhang, Qiaolan Liu, Xiaoting Li","doi":"10.1530/JME-25-0065","DOIUrl":"10.1530/JME-25-0065","url":null,"abstract":"Abstract: Diabetic retinopathy (DR), a prevalent neurovascular complication of diabetes, is a leading cause of blindness in affected individuals. O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation), a unique form of post-translational modification regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase, plays a critical role in cellular processes. This study aimed to investigate the role of OGT-mediated O-GlcNAcylation and its potential regulatory mechanisms in DR. Using a DR mouse model, we evaluated the effect of OGT on retinal tissue damage. An in vitro model was established by treating human retinal endothelial cells (HRECs) with high glucose (HG). The biological behaviors of HRECs were assessed using Cell Counting Kit-8, EdU incorporation, transwell, and tube formation assays. Underlying mechanisms were explored through quantitative real-time PCR, western blot, and co-immunoprecipitation. Our findings revealed that O-GlcNAcylation levels were significantly elevated both in vitro and in vivo. Knockdown of OGT suppressed the proliferation, migration, and angiogenesis of HG-stimulated HRECs, an effect mediated through the upregulation of BAP1. Mechanistically, OGT was found to interact with BAP1 and promote its O-GlcNAcylation, thereby negatively regulating BAP1 expression. Furthermore, OGT knockdown attenuated retinal tissue damage in diabetic mice, an effect dependent on BAP1. In summary, this study reveals a novel role for OGT-mediated O-GlcNAcylation in DR progression, suggesting its potential as a therapeutic target for DR.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856506","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}

引用次数: 0