Aug 2026· Journal of Clinical Endocrinology and Metabolism· 0 citations
Medicine
TL;DR
The temporal decline of circulating miR-1-3p levels and the identification of PKC support a model in which miR-1-3p may contribute to functional maturation of the ZR through modulation of non-canonical intracellular signaling pathways.
Abstract
Context
Adrenarche involves maturation of the adrenal zona reticularis (ZR), but its molecular regulation is poorly understood. MicroRNAs (miRNAs) may contribute to adrenal development.
Objective
To investigate whether circulating miRNAs are associated with ZR maturation during adrenarche and to characterize the functional role of candidate miRNAs in adrenal steroidogenesis.
Design
AND
Setting
Prospective cohort study was nested within the population-based PANIC study with longitudinal follow-up at ages 7, 9, and 15 years, combined with experimental analyses in the human adrenocortical NCI-H295R cell model.
Participants
A total of 34 children (20 girls) with clinical and/or biochemical signs of adrenarche at age 9 as cases, and 24 age-matched controls (11 girls).
Interventions
None.
MAIN OUTCOME MEASURES
Longitudinal serum miRNA expression and in vitro effects of candidate miRNAs on adrenal steroidogenesis and gene expression.
Results
Serum miR-1-3p levels were higher in cases compared to controls at age 7 years (fold change 2, p < 0.001), preceding clinical adrenarche. In both groups, miR-1-3p levels declined during adrenarchal and pubertal development. In vitro, miR-1-3p overexpression increased steroidogenic activity (approximately 1.5-fold on average) without altering the expression of canonical steroidogenic enzyme genes. Transcriptomic analysis identified 208 upregulated and 140 downregulated genes, including PRKCA, encoding protein kinase C (PKC), enriched in the ZR and involved in steroidogenic signaling.
Conclusions
Elevated circulating miR-1-3p precedes clinical adrenarche and enhances steroidogenesis in vitro. The temporal decline of circulating miR-1-3p levels and the identification of PKC support a model in which miR-1-3p may contribute to functional maturation of the ZR through modulation of non-canonical intracellular signaling pathways.
Setmelanotide exerts pleiotropic effects beyond weight reduction, modulating multiple endocrine axes in BBS, and the observed changes highlight MC4R signaling pathway as a key integrator of metabolic and endocrine function and suggest partially weight-independent therapeutic effects.
T. Hühne, E. Steidel, J. Holland et al.· Journal of Clinical Endocrin...· 0 citations
It is indicated that miR-21 could be a potential biomarker for assessing the disease course and metabolic disorders in PCOS and more large-scale studies are needed to validate its diagnostic and prognostic value.
H. Lateef· Al-Kufa University Journal f...· 0 citations
Current understanding of direct actions of FSH and LH on bone, adipose tissue, and brain and focus specifically on the detrimental health burden during and after the menopause: osteoporosis, obesity, and dementia are reviewed.
Se-Min Kim, Funda Korkmaz, Sorang Kang et al.· Endocrine Connections· 0 citations
BACKGROUND
The anorectic peptide nesfatin-1 has been identified as a potential mood regulator. Abnormal nesfatin-1 expression has been observed in both depression animal models and clinical cohorts, but its exact role in depression pathogenesis remains unclear.
AIM
This study aimed to detect peripheral and central nesfatin-1 alterations in rats with chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors, and explore their correlations with hypothalamic-pituitary-adrenal (HPA) axis activity and brainstem monoamine synthesis.
METHODS
Rats were subjected to 5-week CUMS. Enzyme-linked immunosorbent assay (ELISA) quantified plasma mature nesfatin-1 peptide, and Western blot (WB) detected full-length nucleobindin 2 (NUCB2)/nesfatin-1 in the hypothalamus and brainstem. Spearman's rank correlation was performed solely within the CUMS group (n = 6); these exploratory correlational findings require cautious interpretation due to small sample size.
RESULTS
CUMS significantly increased plasma nesfatin-1 as well as hypothalamic and brainstem NUCB2/nesfatin-1. In CUMS rats, plasma nesfatin-1 was positively correlated with corticosterone and forced swim test (FST) immobility time, and negatively correlated with sucrose preference index(SPT) and weight gain. Brainstem NUCB2/nesfatin-1 showed a positive correlation with tryptophan hydroxylase (TPH), while no significant correlation was found between hypothalamic NUCB2/nesfatin-1 and all measured parameters.
CONCLUSION
Chronic stress-induced nesfatin-1 elevation accompanies peripheral HPA hyperactivation and aggravated depressive-like behaviors. Brainstem NUCB2/nesfatin-1 positively correlates with TPH, suggesting NUCB2/nesfatin-1 may link neuroendocrine activity and serotonergic plasticity with the brainstem as a core site. This study provides preliminary correlational evidence for coordinated NUCB2/nesfatin-1 changes across peripheral and central systems under stress-induced depression.
The coordinated alteration of freely circulating and EV-associated miRNAs highlight the potential contribution of miRNA-mediated regulation to premature HPG axis activation and provides a framework for further investigation of the molecular mechanisms underlying pubertal disorders.
Maria Morrou, V. Neocleous, M. Toumba et al.· Frontiers in Endocrinology· 0 citations
Adrenal cortisol-producing adenomas (CPAs) represent the most common endocrine disorder among adrenal incidentalomas and are classified as either subclinical Cushing's syndrome (SCS) or Cushing's syndrome (CS) based on the degree of cortisol hypersecretion. The molecular mechanisms driving hypercortisolism remain poorly understood. To address this, we perform comprehensive proteomic profiling of 9 CS, 10 SCS, and 10 non-functioning adenomas (NFAs). Our analysis reveals a central role for cholesterol metabolic reprogramming in the pathogenesis of CPAs. We observe a progressive gradient of dysregulation in cholesterol metabolic components from NFAs to SCS and CS, mirroring disease severity. A protein panel consisting of low density lipoprotein receptor (LDLR), 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1), hormone-sensitive lipase (LIPE), and synaptophysin (SYP) are identified as a promising combination of candidate pathological markers for CPAs. Importantly, downregulation of calcium binding protein 39 like (CAB39L) is uncovered as a key driver of pathological cortisol production. These findings provide a foundation for protein-based diagnostic and prognostic strategy in CPAs, and highlight the CAB39L signaling pathway as a contributor to disease development.
Xuyang Shi, Yi Yang, Chunxue He et al.· Metabolism: Clinical and Exp...· 0 citations
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