TY - CHAP M1 - Book, Section TI - Glucocorticoid Therapy and Withdrawal A1 - Miller, Walter L. A2 - Kline, Mark W. Y1 - 2018 N1 - T2 - Rudolph's Pediatrics, 23e AB - The receptors for steroids, vitamin D, thyroxine, and many other molecules are zinc-finger transcription factors, which, in the liganded state, bind to specific DNA sequences to modulate gene expression. The half-lives of the encoded RNAs and proteins vary, so that the biological half-life of a steroid hormone varies with the target being considered. There is 1 glucocorticoid receptor gene whose mRNAs are alternatively spliced into numerous forms; these vary in tissue-specific posttranslational modifications and steroid-binding affinity, explaining tissue-specific and interindividual differences in glucocorticoid sensitivity. The nucleotide polymorphism A3669G (rs6198), present in approximately 35% of people, reduces glucocorticoid sensitivity and increases risk for autoimmune disease. ER22/23EK (rs6189/rs6190) (~7% of people) is associated with mild glucocorticoid resistance and a healthier metabolic profile. N363S (rs1695) (~8%) and Bcl1 (rs41423247) (~45%) are associated with mildly increased sensitivity, yielding more body fat, less lean mass, increased insulin resistance, and so on. SN - PB - McGraw-Hill Education CY - New York, NY Y2 - 2024/11/02 UR - accesspediatrics.mhmedical.com/content.aspx?aid=1182920233 ER -