{"title":"Sexual dimorphisms in endocrinopathies: Their impact on the evolution of metabolic diseases","authors":"Chitralekha Kataki","doi":"10.1016/j.mce.2025.112521","DOIUrl":"10.1016/j.mce.2025.112521","url":null,"abstract":"<div><div>Sexual dimorphisms, the biological differences between males and females, are well-documented across various endocrine disorders. These dimorphisms not only influence the presentation and progression of endocrinopathies but also play a critical role in the development and evolution of metabolic diseases. This review explores the intricate relationship between sexual dimorphisms and endocrinopathies such as Diabetes Mellitus, Thyroid disorder, Cushing's syndrome, Addison's disease, polycystic ovary syndrome (PCOS), Hypogonadism in males and acromegaly, and their subsequent effects on metabolic dysfunctions like insulin resistance, obesity, and cardiovascular diseases. By examining the hormonal, genetic, and environmental factors underlying these gender-specific differences, we aim to elucidate how sexual dimorphisms contribute to the disparate prevalence, clinical outcomes, and treatment responses observed in metabolic disorders. This review highlights the significance of considering sexual dimorphisms in advancing the understanding of metabolic diseases.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"601 ","pages":"Article 112521"},"PeriodicalIF":3.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"cFos-mediated β-Arrestin1 in the RVLM alleviates sympathetic hyperactivity induced by ovariectomy","authors":"Jiuqiong Yan , Qi Meng , Fan Hao , Mingjuan Xu","doi":"10.1016/j.mce.2025.112520","DOIUrl":"10.1016/j.mce.2025.112520","url":null,"abstract":"<div><div>Sympathetic hyperactivity is a key feature of cardiovascular dysfunction in postmenopausal women and is closely linked to the onset, progression, and outcomes of cardiovascular events. However, the mechanisms underlying sympathetic nerve hyperactivity due to menopause remain unclear. β-arrestin is a versatile class of intracellular proteins that were initially discovered for their ability to disrupt the G protein-coupled receptors (GPCRs) signaling by binding to activated receptors. A notable reduction in the expression of β-arrestin1 in the rostral ventrolateral medulla (RVLM) associated with increased sympathetic activity and elevated blood pressure (BP) in spontaneously hypertensive rats. It has been reported that the cellular oncogene fos (cFos), as a transcription factor, plays a crucial role in BP regulation. This study aimed to investigate whether β-arrestin1, regulated by cFos in the RVLM, contributes to sympathetic hyperactivity induced by menopause. Bilateral ovariectomy (OVX) was performed to establish a postmenopausal rat model. We found that the expression of β-arrestin1 in the RVLM of OVX rats was reduced, whereas estrogen supplementation increased the expression of β-arrestin1. Furthermore, overexpression of β-arrestin1 in the RVLM of OVX rats attenuated the sympathetic hyperactivity. Conversely, reducing β-arrestin1 expression in the RVLM compromised the cardioprotective effects of estrogen in OVX rats. Additionally, inhibiting the expression of the transcription factor cFos in the RVLM of OVX rats diminished the estrogen-induced increase in the expression of β-arrestin1. These findings suggest that estrogen enhances the expression of β-arrestin1 mediated by cFos in the RVLM of OVX rats, thereby alleviating sympathetic nerve hyperactivity and hypertension.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"601 ","pages":"Article 112520"},"PeriodicalIF":3.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sudipta Dutta , JeHoon Lee , Sakhila K. Banu, Joe A. Arosh
{"title":"New perspectives about the article “Dual inhibition of AKT and ERK1/2 pathways restores the expression of progesterone Receptor-B in endometriotic lesions through epigenetic mechanisms\"","authors":"Sudipta Dutta , JeHoon Lee , Sakhila K. Banu, Joe A. Arosh","doi":"10.1016/j.mce.2025.112496","DOIUrl":"10.1016/j.mce.2025.112496","url":null,"abstract":"","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"602 ","pages":"Article 112496"},"PeriodicalIF":3.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antioxidants improve the viability of diabetic bone marrow MSCs without rescuing their pro-regenerative secretome function","authors":"Michelle Maartens , Mare Vlok , Mari van de Vyver","doi":"10.1016/j.mce.2025.112519","DOIUrl":"10.1016/j.mce.2025.112519","url":null,"abstract":"<div><div>Bone marrow mesenchymal stem cell (BM-MSC) dysfunction and poor viability are prominent in diabetes and limit their therapeutic efficacy. A proteomic investigation was performed to assess disease associated alterations and the efficacy of antioxidants to rescue cellular function. BM-MSCs were isolated from obese diabetic mice (B6.Cg-Lep<sup>ob</sup>/J) cultured in the presence or absence of N-acetylcysteine (NAC) and ascorbic acid-2phosphate (AAP). Label free Liquid Chromatography and Mass Spectrometry (LC-MS) analysis detected 5079 proteins with 251 being differentially expressed between treatment groups. NAC/AAP improved cellular growth/viability post isolation by up-regulating proteins involved in redox status, ATP synthesis, Rho-GTPase signaling and modulated the immunophenotype of BM-MSCs. Despite a single application of the secretome not providing any advantage for wound bed regeneration in full thickness excisional diabetic wounds, the intracellular proteome illustrated the potential mechanisms of action by which NAC/AAP targeted the respiratory chain and modulated the immune phenotype of BM-MSCs. Given these observations, antioxidant supplementation might be more effective as prophylactic strategy to protect MSCs against functional decline instead of using it as a restorative agent and warrants further investigation.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"601 ","pages":"Article 112519"},"PeriodicalIF":3.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
João L. Alves , Rosa M. Quinta-Ferreira , M. Emília Quinta-Ferreira , Carlos M. Matias
{"title":"Exploring different mechanisms of reactive oxygen species formation in hypoxic conditions at the hippocampal CA3 area","authors":"João L. Alves , Rosa M. Quinta-Ferreira , M. Emília Quinta-Ferreira , Carlos M. Matias","doi":"10.1016/j.mce.2025.112517","DOIUrl":"10.1016/j.mce.2025.112517","url":null,"abstract":"<div><div>Hypoxia can lead to severe consequences for brain function, particularly in regions with high metabolic demands such as the hippocampus. Excessive production of reactive oxygen species (ROS) during hypoxia can initiate a cascade of oxidative stress, evoking cellular damage and neuronal dysfunction. Most of the studies characterizing the formation of ROS are performed in the context of ischemia induced by oxygen-glucose deprivation, thus, the role of hypoxia in less severe conditions requires further clarification. The aim of this work was to identify the major mechanisms of ROS generation and assess flavoprotein autofluorescence changes. For ROS detection, the slices were incubated with the indicator H<sub>2</sub>DCFDA, while intrinsic FAD-linked autofluorescence was recorded from indicator free slices. All signals were measured under hypoxia, at the hippocampal mossy fiber synapses of CA3 area, which were chemically stimulated using 20 mM KCl. The results suggest that ROS is formed in the mitochondria, during moderate hypoxia. The blockage of mitochondrial complexes I, III and IV with rotenone, myxothiazol and sodium azide, respectively, and of the mitochondrial calcium uniporter with Ru265, led to the abolishment of ROS changes and to an increase of FAD-linked autofluorescence (with the exception of the complexes III and IV). The blockage of the enzyme oxidases NADPH and xanthine oxidase also impaired ROS formation and rose FAD-linked autofluorescence. Thus, the blockage of any of the steps of the process of ROS formation, namely the activation of critical MRC complexes, calcium entry into the mitochondria, or enzyme oxidases activity, ceases the production of ROS.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"601 ","pages":"Article 112517"},"PeriodicalIF":3.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christina Brummer , Katrin Singer , Kathrin Renner , Christina Bruss , Claus Hellerbrand , Christoph Dorn , Simone Reichelt-Wurm , Wolfram Gronwald , Tobias Pukrop , Wolfgang Herr , Miriam Banas , Marina Kreutz
{"title":"The spleen-liver axis supports obesity-induced systemic and fatty liver inflammation via MDSC and NKT cell enrichment","authors":"Christina Brummer , Katrin Singer , Kathrin Renner , Christina Bruss , Claus Hellerbrand , Christoph Dorn , Simone Reichelt-Wurm , Wolfram Gronwald , Tobias Pukrop , Wolfgang Herr , Miriam Banas , Marina Kreutz","doi":"10.1016/j.mce.2025.112518","DOIUrl":"10.1016/j.mce.2025.112518","url":null,"abstract":"<div><div>Obesity promotes adipose tissue inflammation and leads to impaired local but also systemic immune cell homeostasis. This chronic low-grade inflammation plays a significant role in the development of obesity-associated secondary diseases such as metabolic associated fatty liver disease or cancer. The spleen as the central organ of immune cell regulation is anatomically directly connected to the visceral adipose tissue and the liver via the portal vein circulation. However, the inter-organ crosstalk and linkage between obesity-induced systemic, hepatic and splenic immune cell dysregulation is not clearly outlined. In this study blood, spleen, and liver immune cells of non-obese wildtype vs. leptin deficient obese BTBR mice were isolated and analyzed in terms of leukocyte composition by flow cytometry. Significant differences between circulating, spleen- and liver-resident immune cell distribution revealed, that obesity-induced hepatic and systemic immune cell dysregulation is distinct from splenic immune cell reprogramming. Fatty liver inflammation was associated with splenic myeloid derived suppressor cell (MDSC) and natural killer T cell (NKT) enrichment whereas loss of hepatic T and B cells was not reflected by the splenic lymphocyte landscape. Correlation analysis confirmed a selective strong positive correlation between spleen and liver MDSC and NKT cell distribution indicating that the spleen-liver axis modulates obesity-induced immune dysregulation in a cell-specific manner. Similar results were observed in a diet-induced obesity mouse model. These data provide novel insights into the role of the spleen-liver axis in obesity-induced inflammation and foster the understanding of obesity-associated complications such as fatty liver disease and cancer.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"601 ","pages":"Article 112518"},"PeriodicalIF":3.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bianka M. Zanini , Bianca M. Ávila , Jéssica D. Hense , Driele N. Garcia , Sarah Ashiqueali , Pâmela I.C. Alves , Thais L. Oliveira , Tiago V. Collares , Miguel A. Brieño-Enríquez , Jeffrey B. Mason , Michal M. Masternak , Augusto Schneider
{"title":"Extracellular vesicles from cyclic mice modulate liver transcriptome in estroupause mice independent of age","authors":"Bianka M. Zanini , Bianca M. Ávila , Jéssica D. Hense , Driele N. Garcia , Sarah Ashiqueali , Pâmela I.C. Alves , Thais L. Oliveira , Tiago V. Collares , Miguel A. Brieño-Enríquez , Jeffrey B. Mason , Michal M. Masternak , Augusto Schneider","doi":"10.1016/j.mce.2025.112508","DOIUrl":"10.1016/j.mce.2025.112508","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) of different sizes are secreted by cells and may contain microRNAs (miRNAs) among its cargo. These miRNAs in EVs can induce changes in gene expression and function of recipient cells. In different cells EVs content can change with age and physiological state affecting tissue function. Based on this, the aim of this study was to characterize the miRNA content and role of small EVs (sEVs) from cyclic female mice in the modulation of liver transcriptome in estropausal mice. Two-month-old female mice were induced to estropause using 4-vinylcyclohexene diepoxide (VCD). At six months of age, VCD-treated mice were divided into placebo group (VCD) and sEVs treated group (VCD + sEVs), which received 10 injections at 3-day intervals of sEVs isolated from serum of donor cyclic female mice. A group of cyclic mice also received placebo injection and served as controls (CTL). sEVs injection in mice undergoing estropause had no effect on body mass, insulin sensitivity or organ weight. We observed ten miRNAs differentially regulated in serum sEVs of VCD compared to CTL mice. In the liver we observed 931 genes differentially expressed in VCD + sEVs compared to VCD mice. Interestingly, eight pathways were up-regulated in liver by VCD treatment and down-regulated by sEVs treatment, indicating that sEVs from cyclic mice can reverse changes promoted by estropause in liver. The expression of <em>Cyp4a12a</em>, which is male-specific, was elevated in VCD females but not normalized by sEVs treatment. Our findings indicate that miRNA content in sEVs is regulated by estropause in mice independent of age. Additionally, treatment of estropausal mice with sEVs from cyclic mice can partially reverse changes in the liver transcriptome.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"600 ","pages":"Article 112508"},"PeriodicalIF":3.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luara Jesus Ferrato , Thalles Fernando Rocha Ruiz , Lorena Gabriela de Souza , Gervásio Evangelista Brito-Filho , Simone Jacovaci Colleta , Ellen Cristina Rivas Leonel , Sebastião Roberto Taboga
{"title":"Bisphenol A exposure alters hormonal modulation and responsivity in the prostate of aged female gerbils","authors":"Luara Jesus Ferrato , Thalles Fernando Rocha Ruiz , Lorena Gabriela de Souza , Gervásio Evangelista Brito-Filho , Simone Jacovaci Colleta , Ellen Cristina Rivas Leonel , Sebastião Roberto Taboga","doi":"10.1016/j.mce.2025.112507","DOIUrl":"10.1016/j.mce.2025.112507","url":null,"abstract":"<div><div>The female prostate is a gland regulated by steroid hormones for homeostasis. Bisphenol A (BPA) is an endocrine disruptor related to the progression of malignant lesions in prostate. The aim of this study was to analyze the hormonal modulation and responsiveness of the prostate of aged female gerbils previously exposed to BPA. Females were exposed to 50 μg/kg/day during pregnancy and lactation, and the prostate was analyzed at 18 months of age. Control groups were included to normalize the analysis. The samples were analyzed using histological and immunohistochemical techniques for the expression of androgen (AR), estrogen (ERα and ERβ), prolactin (PRL), and progesterone (PR) receptors, as well as steroidogenic enzymes (5α-reductase and aromatase) and the proliferation (PHH3) and epigenetic (EZH2) markers. Protein quantification was also performed for the receptors and enzymes described, as well as morphological and morphometric analyses of the gland. The results showed an increase in the epithelial expression of AR and ERα and a decrease in the expression of ERβ in this compartment. In addition, a decrease in epithelial expression was observed for the 5α-reductase and aromatase in the prostate epithelium and an increase in the expression of PHH3 and EZH2. By Western blot analyses, significant differences were observed in the protein quantification of the receptors and enzymes described. Thus, the current study showed the role of BPA in intraprostatic hormonal modulation, through alterations in the expression of hormone receptors and the conversion of enzymes in the female prostate, which can lead to the progression of malignant lesions in this tissue.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"600 ","pages":"Article 112507"},"PeriodicalIF":3.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peter J. Fuller , Jun Yang , Morag J. Young , Timothy J. Cole
{"title":"Mechanisms of ligand-mediated modulation of mineralocorticoid receptor signaling","authors":"Peter J. Fuller , Jun Yang , Morag J. Young , Timothy J. Cole","doi":"10.1016/j.mce.2025.112504","DOIUrl":"10.1016/j.mce.2025.112504","url":null,"abstract":"<div><div>The mineralocorticoid receptor plays a central role in homeostasis, mediating the regulation by aldosterone of epithelial sodium transport. In addition, it regulates a range of responses in other tissues where it is likely responding to both mineralocorticoids and glucocorticoids. Structural, functional and evolutionary studies have provided insights into the mechanisms of receptor activation by agonist ligands and how interactions within the domains of the mineralocorticoid receptor may modulate the response to individual ligands including the mechanisms of antagonism. This review will discuss the current understanding, including recent insights into these interactions, with implications for an emerging array of novel non-steroidal compounds targeting the mineralocorticoid receptor; and highlight their relevance to ligand- or tissue-specificity as well as their suitability as therapeutic agents.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"600 ","pages":"Article 112504"},"PeriodicalIF":3.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Renan Orellana-Walden , Ivan Martínez-Díaz , Lisbell Estrada
{"title":"New perspectives about the article “Dual inhibition of AKT and ERK1/2 pathways restores the expression of progesterone Receptor-B in endometriotic lesions through epigenetic mechanisms”","authors":"Renan Orellana-Walden , Ivan Martínez-Díaz , Lisbell Estrada","doi":"10.1016/j.mce.2025.112495","DOIUrl":"10.1016/j.mce.2025.112495","url":null,"abstract":"","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"600 ","pages":"Article 112495"},"PeriodicalIF":3.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}