title: Vitamin D resistant rickets with alopecia: cultured skin fibroblasts exhibit defective cytoplasmic receptors and unresponsiveness to 1,25(OH)2D3.
abstract: A new case of vitamin D dependent rickets (Type II) with alopecia in a 5 yr old child is reported. Skin fibroblasts were propagated in culture and analyzed for cytoplasmic 1,25(OH)2D3 receptors. The rachitic cells failed to exhibit specific, high-affinity binding sites by either Scatchard analysis or sucrose density gradient. Furthermore, a rise in 24-hydroxylase activity could not be elicited following incubation of the rachitig cells with 1,25(OH)2D3. Fibroblasts from a non-rachitic child examined in parallel experiments demonstrated high affinity binding sites (Kd = 0.1 nM, Nmax = 33 fmol/100 micrograms DNA) and the induction of 24-hydroxylase activity. The molecular basis of the unresponsiveness of the cells from the rachitic child appears to be due to defective or absent 1,25(OH)2D3 receptors.
mesh_terms: D000505:Alopecia / Q000209:etiology; D002117:Calcitriol / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D002675:Child, Preschool; D003577:Cytochrome P-450 Enzyme System; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000150:complications / Q000378:metabolism*; D008297:Male; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000187:drug effects / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D013250:Steroid Hydroxylases / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol