Category: receptor_pharmacology
The vitamin D receptor (VDR, NR1I1) is a steroid nuclear receptor activated by 1,25-(OH)₂-vitamin D₃ (calcitriol). 1α-hydroxylation in the kidney (CYP27B1) converts 25-OH-D₃ → 1,25-(OH)₂-D₃; extra-renal 1α-hydroxylation in macrophages, keratinocytes, and other tissues enables autocrine/paracrine VDR signaling. Genomic mechanism: calcitriol binds VDR → VDR-RXR heterodimer → binds VDREs in target gene promoters → coactivator recruitment (DRIP/Mediator, SRC-1, p300) → transcription. Canonical mineral-homeostasis targets: intestinal CaBP-9k + TRPV6 → Ca²⁺ absorption; CYP24A1 → calcitriol catabolism (feedback); renal Ca²⁺ reabsorption; bone osteoblast RANKL → osteoclastogenesis. Pleiotropic non-classical targets: keratinocyte differentiation (calcipotriene for psoriasis); innate immunity (cathelicidin/LL-37 in monocytes — TB defense); adaptive immunity (T-reg induction, Th1/Th17 suppression — autoimmunity modulation); insulin secretion (pancreatic β-cell); cardiovascular (RAAS suppression — VDR-knockout mice have ↑RAAS). Non-genomic / membrane-VDR effects: rapid Ca²⁺/cAMP responses (membrane-associated rapid response steroid binding protein). Therapeutics: cholecalciferol (D₃) + ergocalciferol (D₂) — substrate replacement; calcitriol — direct VDR agonist (renal failure, hypocalcemia); paricalcitol + doxercalciferol — selective VDR analogs (less hypercalcemic); calcipotriene/calcipotriol — topical psoriasis. Cross-links: [[vitamin_d_metabolism]] (upstream synthesis + activation), [[calcium_phosphate_pth_axis]] (mineral homeostasis), [[bone_remodeling_rank_rankl]] (RANKL induction).