Journal of the Endocrine Society最新文献

{"title":"Correction to: \"Disparities in Thyroid Cancer Diagnosis Based on Residence and Distance From Medical Facility\".","authors":"","doi":"10.1210/jendso/bvag132","DOIUrl":"10.1210/jendso/bvag132","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1210/jendso/bvae033.].</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 7","pages":"bvag132"},"PeriodicalIF":4.4,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13306055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Percent body fat misclassifies patients with sarcopenia as obese: support for fat mass index in obesity assessment.","authors":"Susan L Ziolkowski, David R Weber, Joshua F Baker","doi":"10.1210/jendso/bvag139","DOIUrl":"10.1210/jendso/bvag139","url":null,"abstract":"<p><strong>Background: </strong>Percent body fat (%BF) is a common measurement reported on dual-energy X-ray absorptiometry (DXA) to assess for obesity. %BF is calculated as fat mass divided by total body mass, and thereby increases with either higher fat mass or reduced muscle mass. In contrast, fat mass index (FMI; kg/m²) quantifies fat mass independent of muscle mass. It is unknown whether patients classified as obese by %BF have low muscle mass, and whether individuals with sarcopenia are labeled as obese by %BF vs FMI.</p><p><strong>Methods: </strong>We utilized whole-body DXA data from 1999-2006 NHANES in adults ≥20 years of age (<i>N</i> = 14 850) to estimate the prevalence obesity by %BF, FMI, BMI, and waist circumference. We compared body composition across definitions and examined obesity prevalence among those with sarcopenia.</p><p><strong>Results: </strong>More patients met criteria for obesity when defined by %BF (76.8%) compared to BMI (33.9%), FMI (35.8%), and WC (51%). Participants classified as obese by %BF had lower lean (muscle) mass, FMI, and BMI compared to participants obese by FMI (all <i>P</i> < .001). Among patients with sarcopenia, 62.4% were classified as obese by %BF compared with 0.5% if BMI was used to define obesity.</p><p><strong>Conclusion: </strong>Patients who are classified as obese by %BF had the lowest muscle mass and fat mass compared to participants who met other definitions of obesity. The majority of patients with sarcopenia are labeled as obese by %BF. We believe these findings support the use of FMI, a measurement not confounded by muscle mass, for research and clinical assessment.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 8","pages":"bvag139"},"PeriodicalIF":4.4,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13366532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha-klotho, insulin resistance, and adiposity among older adults.","authors":"Anam Ahmad, Michelle Shardell, Rita Rastogi Kalyani, Richard D Semba, Braxton D Mitchell, Toshiko Tanaka, Simeon Taylor, Aman Shrestha, Luigi Ferrucci","doi":"10.1210/jendso/bvag140","DOIUrl":"10.1210/jendso/bvag140","url":null,"abstract":"<p><strong>Context: </strong>Alpha-klotho is a circulating protein linked to better metabolic and aging-related outcomes. However, alpha-klotho's relationship with insulin resistance, and the role of adiposity, remain unclear, especially among older adults.</p><p><strong>Objective: </strong>To evaluate the association of circulating alpha-klotho with measures of insulin resistance and incident diabetes among older adults and examine whether these relationships differ by body mass index (BMI).</p><p><strong>Main outcome measures: </strong>The primary outcome was Homeostatic Model Assessment for Insulin Diabetes (HOMA-IR). Secondary outcomes were serum fasting glucose and insulin, and incident diabetes.</p><p><strong>Design setting and participants: </strong>This secondary analysis examined associations of alpha-klotho with outcomes among 825 community-dwelling adults aged ≥55 years enrolled in the Invecchiare in Chianti Study, a prospective population-based cohort. Alpha-klotho and outcomes were assessed 3 years after enrollment. We performed BMI-stratified regression analysis, with adjustment for covariates, including measures of glucose and insulin taken at enrollment.</p><p><strong>Results: </strong>Among 370 overweight participants (BMI 25.0-29.9 kg/m²), each logarithm unit of alpha-klotho (pg/mL) was associated with 0.51 higher HOMA-IR (95% confidence interval [CI], 0.07-0.94), after covariate adjustment. Alpha-klotho was significantly associated with serum glucose (Beta = 0.56, 95% CI: 0.04-1.09), but not serum insulin after covariate adjustment. No significant associations were found among participants with BMI < 25.0 (<i>n</i> = 279) or ≥30 kg/m² (<i>n</i> = 124) (<i>P</i> for interaction = 0.18). Alpha-klotho was not significantly associated with incident diabetes, overall or in any BMI subgroup.</p><p><strong>Conclusion: </strong>Alpha-klotho was positively associated with insulin resistance, but not incident diabetes, among overweight adults. Findings suggest that alpha-klotho may have a context-dependent relationship with insulin resistance, but not incident diabetes.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 7","pages":"bvag140"},"PeriodicalIF":4.4,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in glucose-regulating neurohormonal pathways-potential impact for type 2 diabetes development.","authors":"Martin H Lundqvist, Maria J Pereira, Urban Wiklund, Susanne Hetty, Jan W Eriksson","doi":"10.1210/jendso/bvag138","DOIUrl":"10.1210/jendso/bvag138","url":null,"abstract":"<p><strong>Aim: </strong>Men have a higher risk to develop type 2 diabetes (T2D) than women. The aim of this study was to investigate if there are sex differences in counter-regulatory hormone dynamics that might affect insulin resistance and hence propensity for T2D. Further, we addressed the roles of sex hormones, menopausal status and metabolic phenotypes for such sex differences.</p><p><strong>Methods: </strong>22 men (7 T2D, BMI 28.8 kg/m²) and 28 women (16 postmenopausal, 9 T2D, BMI 31.5 kg/m²) underwent euglycemic-hyperinsulinemic-hypoglycemic and hyperglycemic clamps with assessments of counter-regulatory hormones and heart rate variability (HRV). Sex hormones (eg, testosterone, estradiol) were analyzed from fasting plasma samples.</p><p><strong>Results: </strong>Men vs women had higher responses of glucagon, ACTH, cortisol and GH but attenuated HRV responses during hypoglycemia and higher ACTH, more sympathetic dominance and lower GH levels during normo- and hyperglycemia. Post- vs premenopausal women had lower GH levels and less favorable HRV profiles but did not otherwise differ. Within-sex correlations between neurohormonal responses and sex hormones were generally weak. In multilinear regressions, M-value and waist-to-hip ratio were the strongest predictors of cortisol, ACTH and GH responses, whereas sex hormones did not explain within- or between-sex variations in neurohormonal responses.</p><p><strong>Conclusion: </strong>In healthy individuals as well as those with obesity or T2D, glucose-dependent counter-regulatory hormonal responses are elevated in men vs both pre- and postmenopausal women. This may contribute to insulin resistance and hence an increased risk of T2D development in men. Central adiposity, but not sex hormone profiles, may partly explain the observed sex differences.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 8","pages":"bvag138"},"PeriodicalIF":4.4,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13351164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear mitochondrial interaction test reveals sex-dependent mitochondrial SNP-Klotho interactions on diabetes risk.","authors":"Tae Jung Oh, Hiroshi Kumagai, Kelvin Yen, Eileen M Crimmins, Thalida E Arpawong, Pinchas Cohen","doi":"10.1210/jendso/bvag143","DOIUrl":"10.1210/jendso/bvag143","url":null,"abstract":"<p><strong>Context: </strong>Environmental or other genetic factors might influence the effect of <i>Klotho</i> (<i>KL)</i> on glucose metabolism.</p><p><strong>Objective: </strong>We investigated mitochondrial genetic variants that interact with <i>KL</i> single nucleotide polymorphisms (SNPs) to modulate diabetes risk.</p><p><strong>Methods: </strong>We used the data from 7047 non-Hispanic White participants of the Health and Retirement Study, a prospective observational study including adults aged 50 years and older from the United States. First, we performed single gene-wide association scans to identify <i>KL</i> SNPs associated with diabetes. Next, we performed a nuclear-by-mitochondrial interaction test (NuMIT) in which we use an identified <i>KL</i> SNP from the gene-wide scan to evaluate potential interactions with 85 mitochondrial SNPs in relation to diabetes.</p><p><strong>Results: </strong>We failed to identify a significant association between diabetes and the <i>KL</i> SNP in our single gene-wide association test. However, we identified a novel variant (<i>KL</i> rs9563121) which showed a trend of increasing Klotho mRNA levels with each additional minor allele. A NuMIT analysis identified mitochondrial SNPs, which showed significant interactions with rs9563121 in relation to diabetes risk. MitoG15929A showed significant interactions with rs9563121 in both men and women. MitoG15929A diminished the potential beneficial effect of <i>KL</i> rs9563121 on diabetes risk in women. Among men with the MitoG15929A variant, <i>KL</i> rs9563121 was associated with higher prevalence of diabetes.</p><p><strong>Conclusion: </strong>The NuMIT approach revealed significant interactions between mitochondrial and nuclear DNA variants of <i>KL</i>. Furthermore, MitoG15929A may have a role in the interaction between diabetes and <i>KL</i> in a sex-dependent manner.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 8","pages":"bvag143"},"PeriodicalIF":4.4,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone density and skeletal turnover in complete androgen insensitivity syndrome.","authors":"Milena Jovanovic, Alexandra Laufer, Deborah Stein, Madeleine E St Ville, Salma Musaad, Sanjay Jumani, Harveen Kaur, Veronica Gomez-Lobo, Catherine M Gordon","doi":"10.1210/jendso/bvag136","DOIUrl":"10.1210/jendso/bvag136","url":null,"abstract":"<p><strong>Context: </strong>Complete androgen insensitivity syndrome (CAIS) is a rare disorder caused by androgen receptor mutations. Due to malignancy concerns, patients historically underwent early gonadectomy, a practice that has come under scrutiny. Data on bone health are limited, especially considering adolescents with intact gonads and after gonadectomy.</p><p><strong>Objective: </strong>This work aimed to investigate bone mineral density (BMD), lean body mass (LBM), and bone turnover in CAIS with intact gonads or after gonadectomy.</p><p><strong>Methods: </strong>Dual-energy x-ray absorptiometry was used to assess BMD and LBM. Serum bone biomarkers and reproductive hormones were measured.</p><p><strong>Results: </strong>Seventeen individuals with CAIS were evaluated, 5 (mean age 27 years) after gonadectomy and 12 (mean age 18 years) with intact gonads. BMD Z-scores trended lower than reference standards, regardless of gonadectomy status. In participants with intact gonads, LBM was positively correlated with spinal BMD Z-score. Procollagen 1 N-terminal propeptides were higher in participants with intact gonads, while osteocalcin levels were lower. There were increased luteinizing hormone and testosterone levels, and decreased estradiol and estrone levels in those with intact gonads. In participants after gonadectomy, BMD Z-scores trended lower. LBM was positively correlated with BMD Z-score at the femoral neck and exercise score with BMD Z-score at the total hip.</p><p><strong>Conclusion: </strong>These findings raise concern that low BMD represents a health risk in all individuals with CAIS, including those with intact gonads and after gonadectomy. Bone remodeling was affected negatively but there was a positive correlation between LBM and BMD. These results underscore the importance of androgens for musculoskeletal health.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 8","pages":"bvag136"},"PeriodicalIF":4.4,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13370833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of propylthiouracil protocols: high-dose monotherapy vs combination of low-dose with iodine.","authors":"Nami Suzuki, Jaeduk Yoshimura Noh, Natsuko Watanabe, Ai Yoshihara, Miho Fukushita, Masako Matsumoto, Masakazu Koshibu, Miki Kawai, Aiko Kitao, Kiminori Sugino, Koichi Ito","doi":"10.1210/jendso/bvag137","DOIUrl":"10.1210/jendso/bvag137","url":null,"abstract":"<p><strong>Background: </strong>Propylthiouracil (PTU) use has decreased due to adverse events (AEs), but it is still needed for patients who cannot tolerate thiamazole.</p><p><strong>Objective: </strong>To compare the efficacy and safety of the PTU protocol between high-dose monotherapy and low-dose combination therapy with potassium iodide (KI).</p><p><strong>Methods: </strong>This is a retrospective observational study including patients who were newly diagnosed with Graves disease (GD) and received PTU as initial therapy between January 2005 and October 2024. Patients who received an initial dose of 300 mg (high-dose group) and those who received 150 mg of PTU combined with 50 mg of KI (low-dose group) were included. The propensity-score matching method was employed to adjust for confounders.</p><p><strong>Results: </strong>A total of 1171 patients (high-dose: low-dose = 1133: 38, all female) with a median age of 32 (interquartile range [IQR]: 28-36) years were included. Median levels of free-thyroxine (FT4) and thyroid-stimulating hormone receptor antibody were 4.97 (IQR: 3.67-7.31) ng/dL, 12.4 (IQR: 6.4-26.8) IU/L. Adverse events occurred in 294 patients (high-dose: low-dose = 289:5). Free-thyroxine levels were significantly lower at Week 2 in the low-dose group than in the high-dose group (<i>P</i> = .014), but the difference disappeared afterwards. The prevalence of inadequate efficacy with the initial dose was significantly higher in the low-dose group (12.8% vs 35.5%, <i>P</i> = .002).</p><p><strong>Conclusion: </strong>Despite a lower rate of efficacy from the initial dose, the low-dose protocol was effective in controlling hyperthyroidism with up-titration in young women with GD, with the potential for fewer AEs.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 7","pages":"bvag137"},"PeriodicalIF":4.4,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13320707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone and joint quality remains impaired in long-term controlled acromegaly: an HR-pQCT study.","authors":"Christian Rosendal, Frederik Østergaard Klit, Annika Vestergaard Kvist, Peter Vestergaard, Jakob Dal","doi":"10.1210/jendso/bvag135","DOIUrl":"10.1210/jendso/bvag135","url":null,"abstract":"<p><strong>Context: </strong>Joint and bone disorders are frequent, disabling complications of acromegaly that progress despite biochemical remission. HR-pQCT provides a precise assessment of bone and joint quality.</p><p><strong>Objective: </strong>To evaluate joint and bone quality in patients with long-term controlled acromegaly.</p><p><strong>Design: </strong>Cross-sectional study.</p><p><strong>Participants: </strong>17 acromegaly patients and 17 age- and sex-matched controls.</p><p><strong>Measures: </strong>HR-pQCT of hand joints, tibia, and radius; bone microindentation; vertebral fracture assessment; dual X-ray absorptiometry; circulating bone biomarkers; questionnaires.</p><p><strong>Results: </strong>Patients with acromegaly (mean age: 61.8 years, mean disease duration: 13.1 years, mean IGF-I xULN: 0.9) had wider joint spaces of the second (2.85 vs 2.68 mm, <i>P</i> = .004) and third (2.92 vs 2.80 mm, <i>P</i> = .037) metacarpophalangeal joints, the latter with a higher risk of osteophytes (50% vs 11.8%, <i>P</i> = .017). Vertebral deformities were more common (88% vs 47%, <i>P</i> = .01), more numerous (2.1 vs 0.7, <i>P</i> < .001), and associated with higher spinal deformity indices (2.6 vs 1.3, <i>P</i> = .04) in participants with acromegaly. HR-pQCT demonstrated lower trabecular bone mineral density in the radius (114.8 vs 150.3 mg/cm³, <i>P</i> = .008) and tibia (129.3 vs 166.2 mg/cm³, <i>P</i> = .002), as well as fewer (1.63 vs 2.11 mm^-1, <i>P</i> = .001) and thinner (0.056 vs 0.064 mm, <i>P</i> = .005) trabeculae. Bone and joint abnormalities increased with age, and the spinal deformity index correlated positively with arthropathy indices, only in the acromegaly group.</p><p><strong>Conclusion: </strong>Long-term, biochemically controlled acromegaly is associated with structural joint alterations and impaired bone microarchitecture, even years after diagnosis.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 7","pages":"bvag135"},"PeriodicalIF":4.4,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13339734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinguishing central precocious puberty from nonprogressive breast development: adiposity and DXA body composition.","authors":"Daniela Fava, Amanda Casirati, Maria Grazia Calevo, Alessia Angelelli, Alessia Pepe, Nadia Gabriella Maiorano, Lucia Acquarone, Chiara Santucci, Claudia Caridi, Valentina Tosto, Marta Panciroli, Caterina Tedesco, Flavia Napoli, Anna Elsa Maria Allegri, Giuseppa Patti, Alessandro Naim, Roberto Gastaldi, Mohamad Maghnie, Natascia Di Iorgi","doi":"10.1210/jendso/bvag134","DOIUrl":"10.1210/jendso/bvag134","url":null,"abstract":"<p><strong>Objective: </strong>Distinguishing central precocious or early puberty (CPP/EP) from nonprogressive premature breast development (npPBD) is challenging, particularly in the context of increasing childhood adiposity, which may affect growth and skeletal maturation independently of hypothalamic-pituitary-ovarian (HPO) axis activation.</p><p><strong>Methods: </strong>We retrospectively evaluated 100 girls (69 CPP/EP, 31 npPBD) and 16 age-matched prepubertal girls with obesity as controls. Assessments included auxology, bone age, hormonal and metabolic profiles, pelvic ultrasound, DXA-derived body composition, and lifestyle factors.</p><p><strong>Results: </strong>Anthropometric parameters and bone age were similar between CPP/EP and npPBD, whereas LH, FSH, estradiol, and IGF-1 SDS (all <i>P</i> < .001) remained the main discriminators between groups. Overall body composition was comparable, except for a higher android-to-gynoid fat ratio in npPBD (<i>P</i> = .03). In both diagnostic groups, overweight/obesity was associated with greater height relative to target height (<i>P</i> = .004 in CPP/EP; <i>P</i> = .03 in npPBD) and higher IGF-1 SDS (<i>P</i> < .001 and <i>P</i> = .02, respectively) compared with controls. Among normal-weight girls, those with CPP/EP showed greater height relative to target height (<i>P</i> = .009) and more advanced bone age (<i>P</i> = .02) than those with npPBD, whereas these differences were not observed in girls with overweight/obesity.</p><p><strong>Conclusion: </strong>Excess adiposity reduces the diagnostic specificity of auxological and skeletal maturation parameters in girls with early breast development. Biochemical assessment remains central, with IGF-1 SDS providing additional supportive information.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 8","pages":"bvag134"},"PeriodicalIF":4.4,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13392474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Placental abundances of IGF1, IGF2, IGFBP2, IGF2R, and PPARα are associated with birth weight.","authors":"Felix Chelslín, Robert Kruse, Karolina Sollie, Lena Erlandsson, Yang Cao, Stefan R Hansson, Maria Lodefalk","doi":"10.1210/jendso/bvag130","DOIUrl":"10.1210/jendso/bvag130","url":null,"abstract":"<p><strong>Context: </strong>The insulin/insulin-like growth factor (IGF) system is a key regulator of fetal growth and placental nutrient regulation.</p><p><strong>Objective: </strong>The objective of this study was to investigate associated gene and protein expressions of the insulin/IGF, adiponectin, and peroxisome proliferator-activated receptor (PPAR) pathways in placenta and cord blood from small-, appropriate-, or large-for-gestational-age (SGA, AGA, LGA) infants and corresponding first-trimester maternal blood.</p><p><strong>Methods: </strong>A total of 60 SGA, 109 AGA, and 55 LGA term infants (birth weight z scores <-2, -2 to +2, and >2, respectively) were included. Placental mRNA expression of 22 genes was analyzed using RT-qPCR. Immunohistochemistry (IHC) was used to determine the protein localization and abundance of 5 differentially expressed genes in 78 representative placental samples. Cord blood and maternal blood concentrations of related proteins were analyzed by ELISA.</p><p><strong>Results: </strong>Placental gene expression of <i>IGF1</i>, <i>IGF2</i>, <i>IGBP2</i>, <i>IGF2R</i>, and <i>PPARA</i> was significantly lower in the SGA group. A moderate correlation in expression levels was observed among differentially expressed genes, except for <i>IGF2R</i>. In the SGA group, IHC staining for IGF1, IGF2, IGF2R, and PPARα was weaker, while IGFBP2 staining was stronger. In the cord blood, the IGF1 and IGF2 concentrations increased successively from the SGA group to the LGA group, whereas the IGFBP2 concentration decreased successively. No differences in maternal blood were observed between the groups.</p><p><strong>Conclusion: </strong>Placental IGF1, IGF2, and PPARα signaling are positively associated with birth weight, whereas that of IGFBP2 is negatively associated, possibly reflecting a shared upstream regulation by nutrition. Conversely, placental IGF2R signaling may aid in normalizing abnormal fetal growth.</p>","PeriodicalId":17334,"journal":{"name":"Journal of the Endocrine Society","volume":"10 7","pages":"bvag130"},"PeriodicalIF":4.4,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13294447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}