Retinoic acid (all-trans + 9-cis) is the bioactive form of vitamin A; binds nuclear RAR (α/β/γ) + RXR (α/β/γ) heterodimers that bind RARE/RXRE on DNA → modulate transcription of genes governing keratinocyte differentiation, sebum production, melanocyte function, and epidermal cell-cycle. Therapeutic retinoids: tretinoin (all-trans RA — topical acne + photoaging; APL induction agent in oncology); isotretinoin (13-cis RA — oral severe nodulocystic acne + sebaceous-gland atrophy; iPLEDGE pregnancy program for teratogenicity); adapalene (RARβ/γ-selective — Differin OTC); tazarotene (RARβ/γ — psoriasis + acne); trifarotene (RARγ-selective — Aklief, truncal acne); bexarotene (RXR-selective — CTCL). Mechanism crosses both DERM + ONC use cases.
Organ Systems
integumentary
endocrine
Pathway Steps
retinol → retinoic-acid — via retinol → retinal (ADH) → retinoic acid (RALDH); cross-link: retinol_vitamin_a_metabolism. Dietary vitamin A (retinol) is oxidized in two steps — to retinaldehyde, then to all-trans retinoic acid (by retinaldehyde dehydrogenases) — the active hormone. This is the committed activation step, and excess retinoid (or the drug isotretinoin) is teratogenic precisely because retinoic acid is so developmentally potent.
retinoic-acid → rar-rxr-heterodimer-activation — via cytoplasmic CRABP transport → nuclear RAR/RXR → RARE binding → transcription change. Retinoic acid binds nuclear retinoic-acid receptors (RARs), which heterodimerize with RXR and bind retinoic-acid response elements to control differentiation and developmental genes. This is exploited therapeutically — ATRA forces differentiation in acute promyelocytic leukemia, and retinoids treat acne and photoaging.