RT Book, Section
A1 Miller, Walter L.
A2 Kline, Mark W.
SR Print(0)
ID 1182920233
T1 Glucocorticoid Therapy and Withdrawal
T2 Rudolph's Pediatrics, 23e
YR 2018
FD 2018
PB McGraw-Hill Education
PP New York, NY
SN 9781259588594
LK accesspediatrics.mhmedical.com/content.aspx?aid=1182920233
RD 2022/08/19
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.