Steroids and One-Carbon Metabolism: Clinical Implications in Endocrine Disorders

Background: One-carbon metabolism (OCM) and steroid metabolism are fundamental biochemical pathways that regulate essential cellular processes and physiological functions. OCM is involved in DNA synthesis, methylation, and redox balance, while steroid metabolism governs the production and degradation of steroid hormones, which notably influence growth, reproduction, and stress responses. Despite their distinct roles, emerging evidence suggests a strong interplay between these two pathways. Summary: This review examines the bidirectional relationship between OCM and steroid metabolism, emphasizing their shared intermediates and cofactors. Folates and methionine, key intermediates of OCM, influence steroid biosynthesis, while the methylation status regulated by OCM affects the expression of steroidogenic enzymes. Conversely, steroid hormones modulate OCM by altering the activity of enzymes in folates and methionine cycles. Disruptions in either pathway are linked to diseases such as cancer, cardiovascular disorders, and neurodegenerative conditions. This narrative review examines the clinical and preclinical data on the interactions between OCM and sex steroids, in both women and men, adrenal steroids and vitamin D metabolism. Key Messages: The interdependence between OCM and steroid metabolism highlights the need to consider both pathways in disease pathogenesis and therapeutic strategies. Their crosstalk plays a crucial role in maintaining cellular homeostasis and responding to metabolic stress. Targeting this metabolic interplay offers new opportunities for treating metabolic disorders, with potential clinical applications in modulating one pathway to influence the other for more integrated disease management.