Journal of Endocrinological Investigation最新文献

Purpose: Increasing evidence suggests a role of 11-oxygenated adrenal androgens (11-OxyA) (11-ketotestosterone, 11KT; 11β-hydroxytestosterone, 11OHT; 11-ketoandrostenedione, 11KA4; 11β-hydroxyandrostenedione, 11OHA4) in several hyperandrogenic disorders. This study aimed to describe distributions of 11-OxyA in a healthy young adult population and explore the relation between hormonal contraceptives and 11-OxyA.

Methods: This study utilized cross-sectional data from the third Fit Futures Study conducted in Norway. 11-OxyA in fasting blood samples were analyzed by liquid chromatography tandem mass spectrometry technique (LC-MS/MS). Contraceptive use was registered and categorized as combined hormonal contraceptives (CHC) or gestagen-only contraceptives. Descriptive statistics were used to report 11-OxyA distributions. Independent t-tests and ANOVA were used to compare biomarker concentrations between groups.

Results: The study included 289 males and 337 females with median age of 27 years. Males had 9-30% higher 11-OxyA concentrations than females (all p's < 0.01). Among the females, 25.5% used CHC, 36.7% used gestagen-only contraceptives, and 37.8% used non-hormonal contraceptives or no contraceptives. As concentrations of 11-OxyA in gestagen-only contraceptives users were similar to non-users, these groups were combined. CHC users had 25-29% lower concentrations of 11KT, 11OHT, and 11KA4 than non-CHC users (all p's < 0.001). After exclusion of CHC users, sex differences attenuated and was no longer significant for 11KT.

Conclusion: Females had lower concentrations of 11-OxyA than males, partly explained by use of CHC, as users had significantly lower concentrations of 11-OxyA than non-CHC users, except 11OHA4. These findings suggest an additional mechanism for CHC in treatment of hyperandrogenic conditions, in which 11-OxyA are elevated.

Purpose: Gestational diabetes mellitus (GDM) significantly threatens maternal and fetal health, necessitating early and accurate diagnostic tools. This study aimed to identify and validate circulating microRNAs (miRNAs) as novel biomarkers for GDM.

Methods: A two-phase cross-sectional study enrolled 55 GDM patients and 55 matched healthy pregnant controls. In the discovery phase, RNA sequencing (RNA-seq) of peripheral blood RNA from a randomly selected subset (5 GDM patients, 5 controls) identified differentially expressed miRNAs. The validation phase employed reverse transcription and quantitative PCR (qPCR) in the entire cohort to confirm identified miR-326 and miR-532-3p expression. Bioinformatics analyses (Gene Ontology [GO] and Kyoto Encyclopedia of Genes and Genomes [KEGG]) investigated their functional roles using a consensus-based approach across multiple databases.

Results: RNA-seq revealed significant upregulation of miR-326 (mean normalized counts = 14.59, P < 0.05; log₂[Fold Change] = 0.93, P < 0.01) and miR-532-3p (mean normalized counts = 46.45, P < 0.05; log₂[Fold Change] = 0.66, P < 0.01) in GDM patients, a finding corroborated by cross-referencing with the Gene Expression Omnibus (GEO) database. qPCR validation confirmed significantly higher expression for both miRNAs in GDM (P < 0.001), with strong negative correlations to fasting, 1-hour and 2-hour postprandial glucose levels. Receiver operating characteristic (ROC) curve analysis revealed excellent diagnostic performance (area under the curve [AUC]: 0.95 [95% CI: 0.91-0.99] for miR-326 and 0.96 [95% CI: 0.93-0.99] for miR-532-3p), robustly confirmed by bootstrap resampling. Functional analyses linked these miRNAs to phosphoinositide 3-kinase (PI3K)/Akt and Rap1 signaling pathways.

Conclusion: This study provides compelling evidence for circulating miR-326 and miR-532-3p as a synergistic pair of biomarkers for GDM. Their high diagnostic accuracy and mechanistic insights into metabolic dysregulation position them as a promising complementary tool for early GDM risk assessment and for understanding GDM pathophysiology.