Abstract
An infant (#99) with ambiguous genitalia was investigated for androgen resistance. Foreskin-derived fibroblasts were normal in respect of: 5α-reductase activity (23 pmol/mg protein/hr); receptor concentration (25 fmol/mg protein); dissociation constant (Kd=0.25 nM); dissociation rate (k−1=6x10−3min-1)of the whole cell DHT-receptor "activity" at 37°C; and thermostability at 42°C.However, preincubation of the fibroblasts from #99 with 3-10 nM DHT for up to 20h (37°C) caused no increase in receptor activity (n-5). In contrast, normal fibroblasts doubled their activity (range of 20h/lh values =1.7-2.8, n=20). This increase is suppressed by 2 μM cycloheximide, and is likely to be a form of “up-regulation” reflecting a larger pool of receptor molecules. A similar up-regulation defect has been observed in another patient with partial AR** in whom the activity showed thermolability and a three-fold greater than normal k−1. The isolated expression of a regulatory defect in #99 indicates: (i) that it is functionally separate from the accompanying thermal and dissociative defects in the other patient; (ii) that 99's mutation probably affected a domain of the androgen receptor molecule that normally acts as the signal for up-regulation.
** Pediatr Res 14 (4,part 2), 483,1980
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bailey, J., Kaufman, M. & Pinsky, L. Defective up-regulation of androgen-receptor activity: a new marker of androgen resistance (AR) in man. Pediatr Res 15, 1543 (1981). https://doi.org/10.1203/00006450-198112000-00051
Issue Date:
DOI: https://doi.org/10.1203/00006450-198112000-00051