The Retinoic-Acid-Related Orphan Receptor Alpha May Be Highly Involved in the Regulation of Seasonal Hair Molting

Seasonal molting in mammals is a crucial survival strategy, yet the underlying molecular mechanisms have not been fully characterized. Melatonin, serving as a bridge for the transmission of photoperiod signals, plays a significant regulatory role in animals' seasonal molting, and the physiological regulatory effects of melatonin signaling are highly dependent on the retinoic-acid-related orphan receptor alpha (<i>Rorα</i>). Hair follicle stem cells (HFSCs) are the most essential cell type in the process of hair follicle regeneration and seasonal replacement. Therefore, this study aims to discuss the regulatory effects of melatonin and its nuclear receptor RORA on HFSCs. This research found that RORA can downregulate cellular proliferation levels by inhibiting the cell cycle of HFSCs, while simultaneously promoting apoptosis in HFSCs and affecting the expression of some genes involved in ferroptosis. RORA can directly bind to the promoter regions of the cyclin genes <i>Ccna2</i> and <i>Ccne1</i> to regulate their transcription. Melatonin may enhance the viability of HFSCs by downregulating RORA levels. In this study, the impact of melatonin and its nuclear receptor RORA on the viability of HFSCs, along with some of the underlying molecular mechanisms, is characterized. These findings provide a theoretical foundation for research on the regulation of animal hair follicle development.