Iron Deficiency Impaired StAR-mediated Steroidogenesis

Iron deficiency (ID) impairs adrenocortical function, yet its underlying mechanism remains unclear. Here, we demonstrate that ID suppresses steroidogenic acute regulatory protein (StAR)-mediated adrenocortical steroidogenesis. In dietary ID mice, deferoxamine-treated mice and H295R cells, mineralocorticoid and glucocorticoid hormone production was significantly reduced. Transcriptomic analysis revealed that ID-induced suppression of steroidogenesis was primarily associated with StAR downregulation, which could be rescued by iron supplementation. Mechanistically, ID activated the ERK signaling pathway, leading to reduced StAR expression. Pharmacological inhibition of ERK restored both StAR protein levels and steroidogenic output. Collectively, our findings suggest that the ERK-StAR axis represents a potential regulatory pathway associated with ID-induced adrenocortical hypofunction.