A and B forms of the androgen receptor are present inhuman genital skin fibroblasts.

Abstract

Two forms of the androgen receptor (AR) protein (apparent molecular masses, are present in human genital skin fibroblasts. The 87-kDa isoform (AR-A) contains an intact C terminus but lacks the normal N terminus found in the 11O-kDa isoform (AR-B).AR-A is the same size as the mutant form of AR produced in fibroblasts from an androgen-resistant individual (R776) by initiation of AR synthesis at the internal Met-188 residue of AR-B. The ratio of AR-B to AR-A in fibroblasts derived from normal individuals is =10:1. The AR isoforms detected in these experiments resemble the A and B f9rms of the human progesterone receptor, which also are encpded by a single gene and differ by the absence or presence of an N-te lsegment. The A and B forms of the human progesterone receptor differ in their ability to activate target genes and are regulated differently in various types ofcells. The identification ofsimilar forms of human AR raises the possibility that AR-A and AR-B also subserve different functions.

The putative androgen receptor-A form results from in vitro proteolysis

“…In agreement with previous reports (Wilson & McPhaul 1994, Gao & McPhaul 1998, AR forms that migrate like AR-A were detected in cell and tissue extracts, particularly in frozen extracts prepared in the absence of dihydrotestosterone (DHT). By the analysis of several AR mutants and the use of anti-peptide antibodies specific to different regions of the AR and extraction conditions that minimize proteolysis, the data indicate that the previously described 87 kDa AR-A and forms with similar migration by SDS gel electrophoresis result from in vitro proteolysis of the NH 2 -or carboxyl-terminal region.…”

“…2A, lane 1, pCMV5) when transfected with the parent vector that lacked AR coding sequence as previously reported (Kaighn et al 1979, Tilley et al 1990. Since the electrophoretic migration of both smaller forms was similar to that of the previously described 87 kDa AR-A (Wilson & McPhaul 1994, Gao & McPhaul 1998, we investigated their origin and domain composition.…”

“…An 87 kDa AR-A lacked part of the NH 2 -terminal region analogous to PR-A and comigrated with an expressed fragment that initiated at the second methionine at residue 189 (Wilson & McPhaul 1994). A survey of tissues indicated different ratios of the two AR forms, but in contrast to PR, the amounts of AR-A were only 10% of the amount of intact AR (Wilson & McPhaul 1996, Gao & McPhaul 1998.…”

“…A survey of tissues indicated different ratios of the two AR forms, but in contrast to PR, the amounts of AR-A were only 10% of the amount of intact AR (Wilson & McPhaul 1996, Gao & McPhaul 1998. It was postulated that, like PR, AR-A occurs in vivo and has functional properties distinct from full-length AR (Wilson & McPhaul 1994, Gao & McPhaul 1998. Previous studies relied in part on AR expression where the sequence flanking the second methionine was altered to increase initiation at this position (Gao & McPhaul 1998).…”

The molecular basis of male sexual differentiation

“…The predominantly used open reading frame encodes for a protein migrating at about 110 kDa consisting of between 910 (51) and 919 (54) amino acids. However, in various genital and non-genital tissues, a different 87 kDa isoform of the AR has been detected, comprising about 4-26% of the total AR protein level (55)(56)(57). With respect to similar observations on the progesterone receptor (PR), these isoforms have been termed AR-B (110 kDa) and AR-A (87 kDa) respectively.…”