retinoids

Retinoids are a class of chemical compounds derived from vitamin A or synthetic analogs that regulate cell growth, differentiation, and apoptosis. They exert their biological effects mainly through nuclear receptors, notably the retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Activation of these receptors modulates transcription of genes involved in skin cell turnover, immunity, and development.

Natural forms and metabolism: Vitamin A includes retinol (alcohol), retinal (aldehyde), and all-trans-retinoic acid (active metabolite). Retinyl esters are stored in the liver and mobilized as needed. In circulation, vitamin A is transported bound to retinol-binding protein (RBP4). Cellular uptake involves binding proteins such as CRBP, and retinol is sequentially oxidized to retinal and then to retinoic acid, which cannot be converted back and thus regulates gene expression.

Mechanism of action: Retinoic acid binds RARs, and 9-cis-retinoic acid binds RXRs, with heterodimers regulating transcription of target genes. The signaling influences keratinocyte differentiation, cell proliferation, lipid metabolism, and immune responses, contributing to skin remodeling and normal development.

Uses and applications: In dermatology, topical retinoids such as tretinoin, adapalene, and tazarotene are used for acne, photoaging, and fine lines. Systemic retinoids, including isotretinoin for severe nodular acne and acitretin for psoriasis, are employed in more extensive disease. In oncology, all-trans retinoic acid (ATRA) induces differentiation in acute promyelocytic leukemia. Some retinoids are used cosmetically for anti-aging effects, though results vary.

Safety and monitoring: Teratogenic risks with systemic retinoids require strict pregnancy prevention programs and counseling. Adverse effects include mucocutaneous dryness, irritation, and photosensitivity; systemic retinoids can cause hepatotoxicity, lipid elevations, and rare mood or bone changes. Interactions and cumulative irritation should be considered, and liver function and lipid levels often require monitoring with systemic therapy.