Molecular and Cellular Endocrinology最新文献

{"title":"Hsp90α as a promising therapeutic target for suppressing tumor progression in Lactotroph PitNETs","authors":"Jie Wu,&nbsp;Zhengan Zhou,&nbsp;Chongxue Ding,&nbsp;Hongjie Sun,&nbsp;Ming Xia,&nbsp;Kai Zhou,&nbsp;Tingrong Zhang,&nbsp;Shaoshan Li","doi":"10.1016/j.mce.2026.112733","DOIUrl":"10.1016/j.mce.2026.112733","url":null,"abstract":"<div><h3>Background</h3><div>Aggressive Lactotroph Pituitary Neuroendocrine Tumors (Lactotroph PitNETs) usually exhibit invasive growth behavior and resistance to dopamine agonists, showing difficulty in radical treatment and a high recurrence rate. Heat shock protein 90α(Hsp90α),a pivotal isoform of the heat shock protein 90(Hsp90) family, acts as a central chaperone that stabilizes numerous oncoproteins driving tumor progression, but its role in Lactotroph PitNETs remains unclear.</div></div><div><h3>Objective</h3><div>To study the effect of Hsp90α knockdown on the proliferation and invasiveness of Lactotroph PitNETs cells (MMQ).</div></div><div><h3>Methods</h3><div>Hsp90α and EGFR expression was compared between 18 aggressive and 22 Non-Aggressive human Lactotroph PitNETs by IHC and immunofluorescence. MMQ rat lactosomatotroph cells were transduced with lentiviral shRNA targeting Hsp90α(shHsp90α). Cell proliferation (CCK8),apoptosis (Annexin-V/7-AAD flow cytometry), Prolactin (PRL) secretion (ELISA), migration and invasion (Transwell) were assessed. Western blotting evaluated EGFR,<strong>PRL</strong>,AKT,ERK1/2,mTOR,p-AKT,p-ERK1/2 and p-mTOR.</div></div><div><h3>Results</h3><div>Aggressive Lactotroph PitNETs displayed higher Hsp90α and EGFR expression and showed a notable degree of spatial overlap. Hsp90α knockdown reduced EGFR,AKT,ERK1/2,mTOR,p-AKT,p-ERK1/2 and p-mTOR levels, decreased proliferation, increased apoptosis, lowered PRL secretion, and impaired migration and invasion.</div></div><div><h3>Conclusions</h3><div>Hsp90α knockdown simultaneously destabilizes EGFR and its downstream AKT/mTOR and ERK axes, resulting in multi-modal suppression of Lactotroph PitNETs invasion. Targeting Hsp90α may offer a novel therapeutic strategy for Aggressive Lactotroph PitNETs refractory to standard medical therapy.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"614 ","pages":"Article 112733"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145979822","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":"Exploring recent insights on intermittent fasting in regulating glucocorticoid levels and diet-induced metabolic disorders with focus on MAFLD and hepatic outcomes","authors":"Jasper Okoro Godwin Elechi ,&nbsp;Carolina Ramos de Mendonça ,&nbsp;Vitor Carlos de Araújo Bandeira ,&nbsp;Maria Surama Pereira Da Silva ,&nbsp;Ana Paula Rocha de Melo ,&nbsp;Rubem Carlos Araujo Guedes ,&nbsp;Sandro Massao Hirabara ,&nbsp;Erika Cione ,&nbsp;Diogo Antonio Alves de Vasconcelos","doi":"10.1016/j.mce.2026.112736","DOIUrl":"10.1016/j.mce.2026.112736","url":null,"abstract":"<div><div>Consumers' risky eating behaviours aided by the current food environment have led to an increase in diet-related metabolic disorders. Metabolic (dysfunction)-associated fatty liver disease origin represents a major global health burden that is increasing at an alarming rate on an annual basis. Modifying the timing of calorie consumption, dietary composition, or caloric intake offers a promising therapeutic approach for the management of this condition. The aim of this review was to provide a concise analysis of the impact of intermittent fasting on the regulation of glucocorticoid levels and diet-induced metabolic disorders with a focus on non-alcoholic fatty liver diseases. We found that intermittent fasting primarily regulates hepatic autophagy via nutritional and hormonal pathways, aiding in the maintenance of energy equilibrium, enhancement of mitochondrial function, regulation of liver quality, preservation of cellular homeostasis, protection of cells from harmful factors, mitigation of liver metabolic disorders, and improvement of liver inflammation. Also, the physiological changes induced by intermittent fasting and their metabolic consequences arise through multiple mechanisms, including alterations in hepatic metabolism, hepatic autophagy, inflammatory responses, liver functional enzymes, hepatic steatosis, fibroblast growth factor signalling, White adipoe tissue browning, adipokines, circadian rhythms, lipid profiles, body composition, the adipose tissue–gut microbiome axis, skeletal muscle, and the autophagy process. Interestingly, we identified the complex interplay among glucocorticoids, intermittent fasting, and non-alcoholic fatty liver diseases highlighting the hepatic macrophage glucocorticoid receptor as a pivotal mediator of fasting-induced reprogramming of the macrophage secretome, including fasting-suppressed cytokines. In conclusion, existing data indicates that intermittent fasting in patients with non-alcoholic fatty liver diseases is a viable, safe, and successful strategy for weight reduction, demonstrating notable trends in the amelioration of dyslipidaemia and non-alcoholic fatty liver diseases.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"614 ","pages":"Article 112736"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003723","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":"Toward intelligent hormonal diagnostics: Quantum dots reshaping endocrine disease detection","authors":"Sara Gemini-Piperni ,&nbsp;Temitope Aribigbola ,&nbsp;Marjorie Dardis Murucci ,&nbsp;Zakariyya Muhammad Bello ,&nbsp;Alana da Cunha Goldstein ,&nbsp;Oluwatosin Stella Olayinka ,&nbsp;Tran Nhat Phong Dao ,&nbsp;Rômulo Sperduto Dezonne ,&nbsp;Sunday Amos Onikanni ,&nbsp;Leandro Miranda-Alves","doi":"10.1016/j.mce.2025.112722","DOIUrl":"10.1016/j.mce.2025.112722","url":null,"abstract":"<div><div>Endocrine disorders necessitate diagnostic platforms capable of detecting rapid, low-abundance, fluctuating hormonal signals with high precision. Quantum dot (QD) technology has revolutionized this field by enabling multiplexed, ultrasensitive, and real-time biochemical profiling. Unlike traditional immunoassays limited to single-analyte detection and signal decay, QDs offer exceptional photostability, quantum-level sensitivity, and tunable emission, allowing simultaneous monitoring of various hormonal biomarkers related to thyroid, pancreatic, adrenal, and reproductive dysfunctions. Recent advancements have combined QDs with AI-assisted signal decoding, microfluidics, and wearable biosensor interfaces, creating intelligent systems capable of predicting trends rather than providing static measurements. Functionalized QDs engineered with aptameric, peptidic, or antibody-based recognition domains have shown promising diagnostic capabilities for insulin, estradiol, and thyroid hormones in complex biological samples. As biocompatible QD formulations continue to evolve, their integration with digital health platforms positions them as the next frontier in continuous endocrine monitoring, early disease detection, and personalized hormonal medicine. This review highlights key technological advancements, translational hurdles, and future directions necessary to propel QD-enabled endocrine diagnostics from the laboratory to clinical practice.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"613 ","pages":"Article 112722"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145841087","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":"Integrative advances in endocrine oncology: From unique glimpses to familiar themes","authors":"Shereen Ezzat","doi":"10.1016/j.mce.2025.112723","DOIUrl":"10.1016/j.mce.2025.112723","url":null,"abstract":"<div><div>The field of endocrine oncology is benefiting from broad advances based on key insights in the pathogenesis of neoplasia. While traditionally regarded as unique and distinct entities from non-endocrine neoplasias, deeper molecular profiling studies of endocrine tumors are now challenging this dogma. In this group of papers, experts from across the field provide their perspectives. Each group focuses on a different endocrine gland which they use as a model that highlights the spectrum of disease behavior. It is hoped that collective reflection on these vignettes will reveal new opportunities that can facilitate more effective detection and therapeutic approaches.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"613 ","pages":"Article 112723"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878657","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":"EGR1 promotes ferroptosis in endometriosis through transcriptional activation of HMOX1","authors":"Fan Yang ,&nbsp;Duo Liu ,&nbsp;Liuting Hu ,&nbsp;Hao Tan ,&nbsp;Yajing Wei ,&nbsp;Ruyu Yang ,&nbsp;Biqi Huang ,&nbsp;Qiuyu Zou ,&nbsp;Qiong Wu ,&nbsp;Yushi He ,&nbsp;Huaxi Mai ,&nbsp;Xi Lan ,&nbsp;Ying Yan ,&nbsp;Zixuan Huang ,&nbsp;Xinyan Huang ,&nbsp;Zhuangzhi Fu ,&nbsp;Zhiyun Deng ,&nbsp;Qinghua Huang ,&nbsp;Shuzhong Yao ,&nbsp;Yanchun Liang","doi":"10.1016/j.mce.2025.112721","DOIUrl":"10.1016/j.mce.2025.112721","url":null,"abstract":"<div><div>Endometriosis (EM) affects approximately 10% of women of reproductive age and remains a prevalent estrogen-dependent gynecological disorder with limited therapeutic efficacy and high recurrence rates. Ferroptosis—an iron-dependent, non-apoptotic form of regulated cell death driven by lipid peroxidation—has recently been recognized to play a paradoxical role in EM pathogenesis. To explore ferroptosis-related mechanisms in EM, this study integrated transcriptomic profiling from five Gene Expression Omnibus datasets (GSE6364, GSE7305, GSE11691, GSE23339, GSE51981) with machine learning algorithms and functional validation. Bioinformatic analysis identified 19 ferroptosis-related differentially expressed genes, with hub genes prioritized through protein-protein interaction network analysis. LASSO regression, support vector machine, and random forest models collectively identified EGR1, HMOX1, TIMP1, and FABP4 as robust diagnostic biomarkers, with strong performance in receiver operating characteristic analysis. Clinical validation confirmed significant upregulation of EGR1 and HMOX1 in ectopic endometrial tissues. Functional assays in 12Z endometriotic cells showed that EGR1 silencing partially attenuated erastin-induced ferroptosis by restoring mitochondrial membrane potential, reducing lipid peroxidation, and modulating key ferroptosis markers. Mechanistically, JASPAR analysis predicted EGR1 binding to conserved motifs in the HMOX1 promoter, which was validated using chromatin immunoprecipitation quantitative PCR and dual-luciferase reporter assays. Together, these results identify the EGR1/HMOX1 axis as a novel regulatory hub in EM-associated ferroptosis, offering new insights into diagnostic biomarkers. Therefore, targeting this axis may disrupt iron-redox crosstalk, offering a promising therapeutic avenue to mitigate endometriosis progression.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"613 ","pages":"Article 112721"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145805008","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":"CD36 may regulate glycolytic and steroidogenic processes but not the fatty acid uptake in bovine granulosa cells","authors":"Xuelian Tao,&nbsp;Marten Michaelis,&nbsp;Julia Brenmoehl,&nbsp;Jens Vanselow,&nbsp;Vijay Simha Baddela","doi":"10.1016/j.mce.2025.112717","DOIUrl":"10.1016/j.mce.2025.112717","url":null,"abstract":"<div><div>Postpartum metabolic stress increases non-esterified fatty acid (NEFA) concentration in follicular fluid, thereby impairing oocyte and granulosa cell (GC) function. CD36, a multifunctional scavenger receptor, is involved in the uptake of NEFAs in various cell types. This study examines lipid droplet (LD) accumulation and <em>CD36</em> expression in GCs treated with oleate (OA), palmitate (PA), stearate (SA), and their combination. We also explored the role of <em>CD36</em> in lipid uptake, glucose metabolism, and steroidogenesis in GCs. Flow cytometry analysis revealed that SA, OA, and the combined NEFA treatments resulted in significant LD accumulation, while PA had a minimal effect. Interestingly, <em>CD36</em> expression mirrored the levels of LD accumulation in all treatments. However, <em>SLC27A1</em>, another highly expressed NEFA transporter, was upregulated by SA but was unchanged by PA and OA treatments. Combination of OA, PA, and SA has increased both <em>CD36</em> and <em>SLC27A1</em> expression. OA treatment induced a dose-dependent increase in LD accumulation and <em>CD36</em> expression. However, <em>CD36</em> knockdown did not affect either LD accumulation or triglyceride levels, indicating that <em>CD36</em> is not essential for NEFA uptake, despite its increased expression. Previously, we showed that OA enhances glycolysis in GCs; here, we found that <em>CD36</em> is involved in glucose metabolism as its silencing significantly reduced the extracellular acidification rate and mitochondrial membrane potential in GCs. Furthermore, <em>CD36</em> knockdown significantly reduced progesterone production. These findings suggest that while <em>CD36</em> is dispensable for NEFA uptake, it may play a regulatory role in maintaining glycolytic activity, mitochondrial function, and steroidogenesis in GCs under elevated NEFA levels.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"613 ","pages":"Article 112717"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752012","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":"Prenatal perfluorooctanoic sulfonate exposure is associated with polycystic ovary syndrome-like and related traits in female offspring mice","authors":"C. Urrutia-Lopez ,&nbsp;L. González-Carranza ,&nbsp;A. Barajas-Salinas ,&nbsp;E. Bonilla ,&nbsp;J.J. Rodriguez-Mercado ,&nbsp;A. Aviles ,&nbsp;E. Langley ,&nbsp;J.P. Reyes-Grajeda ,&nbsp;F. Casillas ,&nbsp;A. Lopez ,&nbsp;E. Casas ,&nbsp;M. Betancourt ,&nbsp;M.C. González-Torres ,&nbsp;I. Bahena-Ocampo","doi":"10.1016/j.mce.2025.112707","DOIUrl":"10.1016/j.mce.2025.112707","url":null,"abstract":"<div><div>Polycystic Ovary Syndrome (PCOS), is the most common female endocrine disorder affecting women of reproductive age. Its prevalence is estimated to be up to 13 % worldwide. This heterogeneous clinical condition is characterized by marked clinical and/or biochemical hyperandrogenism, ovulatory dysfunction, and frequent development of polycystic ovaries. Several studies have focused on the relationship between endocrine-disrupting pollutants and PCOS development. Perfluorooctanesulfonate (PFOS) is ubiquitously detected in the environment. Exposure to endocrine-disrupting chemicals, including PFOS, during early fetal development may lead to alterations similar to the PCOS phenotype. Using mice as a model, we compared the effects of prenatal exposure to PFOS or dihydrotestosterone (a model of PCOS induction). After analyzing steroid status, we detected delayed pubertal onset accompanied by increased testosterone concentrations in adulthood, as well as altered estrous cycles with a longer metestrus phase. At this point, two of three Rotterdam criteria have been confirmed as PCOS features. Finally, we identified endocrine disruption in the ovaries from adult females prenatally exposed to PFOS, as evidenced by altered expression of genes involved in steroidogenesis pathways, as well as altered expression of gonadotropin hormone receptors, and Amh signaling. These data support a role of PFOS in endocrine disruption and in promoting development of PCOS symptom development.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"613 ","pages":"Article 112707"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743426","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":"Bone marrow transplantation attenuates inflammation and improves glycemic control in type 2 non-obese diabetic Goto-Kakizaki rats","authors":"João Carlos de Oliveira Borges ,&nbsp;Ilana Souza Correa ,&nbsp;Gabriela Mandú Gimenes ,&nbsp;Liliane de Araújo Ferreira ,&nbsp;Maria Andréa Rodrigues de Moura Silva ,&nbsp;Janaina Ribeiro Barbosa Pauferro ,&nbsp;Tiago Bertola Lobato ,&nbsp;Amara Cassandra dos Anjos Alves ,&nbsp;Ana Carolina Gomes Pereira ,&nbsp;Karolayne Oliveira Souza ,&nbsp;Camila Soares dos Santos ,&nbsp;Adriana Cristina Levada- Pires ,&nbsp;Tania Cristina Pithon-Curi ,&nbsp;Gabriel Nasri Marzuca-Nassr ,&nbsp;Sandro Massao Hirabara ,&nbsp;Rui Curi ,&nbsp;Renata Gorjão ,&nbsp;Laureane Nunes Masi","doi":"10.1016/j.mce.2025.112716","DOIUrl":"10.1016/j.mce.2025.112716","url":null,"abstract":"<div><div>Chronic hyperglycemia induces changes in the bone marrow (BM) microenvironment, favoring the expansion and differentiation of stem cells toward a pro-inflammatory profile. Since leukocyte recruitment plays a key role in chronic inflammation during the onset of type 2 diabetes mellitus (T2DM), the aim of this study was to evaluate the influence of bone marrow transplantation (BMT) on glycemic control and inflammatory markers in Goto-Kakizaki (GK) rats transplanted after weaning. GK rats are spontaneously non-obese, T2DM animals. We performed BMT from normoglycemic Wistar (WT) rats to GK animals (aged 28 days), previously immunosuppressed with busulfan (20 mg/kg) and cyclophosphamide (150 mg/kg). The mRNA expression of pro-inflammatory cytokines IL-1β and IL-7 was increased in the BM of weaned GK rats, and it was reduced in the BM mononuclear cells (BMMCs) 100 days after BMT. Hepatic cytokine levels were also evaluated by flow cytometry to calculate the Inflammatory Marker Index (based on IFN-γ, TNF-α, IL-6, and IL-10), which was decreased in transplanted GK rats. Moreover, transplanted GK rats also showed reduced fasting glucose evaluated at 30, 60, and 90 days after transplantation. BMT also induced a significant decrease in plasma insulin and attenuated insulin resistance (HOMA-IR). Overall, BMT in just-weaned GK rats, characterized by an elevated inflammatory profile in the BM and liver, culminated in improvement of glycemic control compared with non-transplanted GK animals. In conclusion, modulation of the BM microenvironment emerges as a novel therapeutic avenue for managing non-obese T2DM and preventing its complications.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"613 ","pages":"Article 112716"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145718887","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":"Endocrine programming of the pituitary–thyroid–adrenal axis: Sex-Specific effects of maternal malnutrition in rats","authors":"Ana Lívia Silvério Vieira,&nbsp;Gustavo Monezzi Cordeiro,&nbsp;Vinicius Alexandre de Andrade Felipe,&nbsp;Matheus Naia Fioretto,&nbsp;Luísa Annibal Barata,&nbsp;Marina Pereira Pires,&nbsp;Pedro Menchini Vitali,&nbsp;Renato Mattos,&nbsp;Isabelle Tenori Ribeiro,&nbsp;Flávia Alessandra Maciel,&nbsp;Hecttor Sebastian Baptista,&nbsp;Luis Antonio Justulin","doi":"10.1016/j.mce.2025.112715","DOIUrl":"10.1016/j.mce.2025.112715","url":null,"abstract":"<div><div>The Developmental Origins of Health and Disease (DOHaD) concept highlights that early-life development can be influenced by environmental factors, leading to long-term metabolic programming in the offspring. Maternal Protein Restriction (MPR) is a well-established model within this framework, inducing cellular stress and hormonal imbalances that disrupt basal metabolic regulation in descendants. We aim to investigate the consequences of MPR (6 %) on the metabolism and the pituitary-thyroid-adrenal axis of male and female postweaning rats. Systemically, there was a decrease in hormones T3 and T4 in the males and a decrease in T4 in the females. In the pituitary, we observed an increase in the <em>Ppar a</em>, <em>Ppar g</em>, and <em>Neurod1</em> gene expression and a decrease in the <em>Prl</em> gene in the males of the GLLP group, while females exhibited a decrease in the <em>Pomc</em> and <em>Ir</em> gene expression. In the thyroid, male rats showed an increase in the <em>Tshr</em> and <em>Ar</em> gene expression. In gene expression of adrenal glands, we observed an increase in the expression of the <em>Sts</em> gene in males and a decrease in <em>Cyp21a2</em> and <em>Mao</em> in females. In silico analyses demonstrated the potential sex-specific disturbance of MPR, mainly on developmental biology, endocrine response, endoplasmic reticulum, and endocytic pathways, indicating a risk scenario for endocrine diseases. Therefore, we conclude that MPR directly affects the early functioning of the pituitary–thyroid–adrenal axis in a sex-specific manner, highlighting its role in metabolic programming and the developmental origins of endocrine disorders.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"613 ","pages":"Article 112715"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774969","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":"Estrogen therapies enhance mammary carcinogenesis in aging gerbil females under endocrine disruption","authors":"Thalles Fernando Rocha Ruiz ,&nbsp;Stella Bicalho Silva ,&nbsp;Vitor Grigio ,&nbsp;Paula Rahal ,&nbsp;Marília de Freitas Calmon ,&nbsp;Patrícia Simone Leite Vilamaior ,&nbsp;Ellen Cristina Rivas Leonel ,&nbsp;Sebastião Roberto Taboga","doi":"10.1016/j.mce.2025.112720","DOIUrl":"10.1016/j.mce.2025.112720","url":null,"abstract":"<div><div>Breast cancer is closely associated with the hormonal sensitization that the mammary gland (MG) undergoes. We evaluated the effects of endogenous (E2) and synthetic (EE2) estrogens, commonly used as hormonal therapies during menopause, in a context of a pro-carcinogenic environment of endocrine disruption. This scenario was modeled to mimic the menopausal involution of the MG during aging in the Mongolian gerbil experimental model under previous bisphenol A exposure, during pregnancy and lactation. Our findings revealed significant remodeling of the epithelial compartment, characterized by increased branching density and loss of normal features, including decreased CD117+ luminal cells and loss of E-cadherin expression. Hormonal therapy with E2 or EE2 led to the development of epithelial lesions, characterized by an increase in invasive microcarcinomas and a decrease in basal (p63+α-SMA-) and myoepithelial (p63+α-SMA+) progenitor cells, contributing to increased neoplastic invasiveness. These changes were orchestrated by overexpression of EZH2 and a decrease in BRCA1, indicating a poor prognosis, especially for EE2. Furthermore, an imbalance between proliferation (PH-H3⁺ cells) and apoptosis (cleaved caspase 3) was observed in the MG of females treated with E2 and EE2. Additionally, distinct hormone receptor profiles were identified, with consistent upregulation of ERα and concomitant downregulation of ERβ and PR, particularly in EE2-treated MG. These alterations may contribute to the observed dysregulation of proliferation and apoptosis. Our results demonstrate that estrogenic hormonal therapies promote neoplastic progression of the aging MG previously subjected to endocrine disruption.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"613 ","pages":"Article 112720"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788626","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}