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MicroRNAs (miRNAs) may contribute to adrenal development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate whether circulating miRNAs are associated with ZR maturation during adrenarche and to characterize the functional role of candidate miRNAs in adrenal steroidogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design and setting<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions<\/jats:title>\n                    <jats:p>None.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main outcome measures<\/jats:title>\n                    <jats:p>Longitudinal serum miRNA expression and in vitro effects of candidate miRNAs on adrenal steroidogenesis and gene expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Serum miR-1-3p levels were higher in cases compared to controls at age 7 years (fold change 2, P &amp;lt; .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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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 noncanonical intracellular signaling pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgag341","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T11:32:31Z","timestamp":1787052751000},"source":"Crossref","is-referenced-by-count":1,"title":["Circulating miR-1-3p precedes adrenarche and modulates adrenocortical steroidogenesis via protein kinase C signaling"],"prefix":"10.1210","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6076-1512","authenticated-orcid":false,"given":"Jani","family":"Liimatta","sequence":"first","affiliation":[{"name":"Kuopio Pediatric Research Unit (KuPRU), Institute of Clinical Medicine, University of Eastern Finland , Kuopio 70210 ,","place":["Finland"]},{"name":"Department of Pediatrics, Kuopio University 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