Androgen receptor in rat liver: characterization and separation from a male-specific estrogen-binding protein.
Many liver processes are sexually dimorphic. In particular, the microsomal content of specific enzymes and the synthesis of specific proteins are under sex steroid hormone control. Because the liver of male rats is strikingly androgen responsive, we sought evidence for an androgen receptor in this tissue. We detected and characterized both cytosolic and nuclear androgen-binding proteins. Both forms bind [3H]R1881 (methyltrienolone, 17 beta-hydroxy-17 alpha-methyl-4,9,11-estratriene-3-one) with the high affinity, low capacity, and specificity for androgens and antiandrogens characteristic of androgen receptors. No high-affinity binding of [3H]DHT could be detected in unfractionated cytosol because of the rapid metabolism of this ligand; however, binding of a DHT metabolite to the high-capacity male-specific estrogen binder (MEB) of cytosol was observed. Both gel filtration and heparin-Sepharose affinity chromatography separate the cytosolic androgen receptor from MEB. Incubation of cytosol in the absence of sodium molybdate resulted in androgen-binding activity which was retained by DNA-cellulose. Castration of male rats results in a time-dependent loss of both cytosolic and nuclear androgen binding, as well as a loss in MEB activity. Androgen-binding activity is low in livers from female rats, but can be induced by testosterone treatment. An intact pituitary is necessary for maintenance of androgen-binding activity, as hypophysectomy results in complete loss of activity.
Veterans Administration Medical Center, Pittsburgh, Pennsylvania 15240.
P K
PK
Eagon
S M
SM
Seguiti
B J
BJ
Rogerson
T F
TF
McGuire
L E
LE
Porter
D H
DH
Seeley
D000818:Animals; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D004963:Estrenes / Q000378:metabolism; D005260:Female; D007016:Hypophysectomy; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D015741:Metribolone; D009919:Orchiectomy; D010052:Ovariectomy; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000302:isolation & purification / Q000378:metabolism*; D011960:Receptors, Estrogen; D012016:Reference Values; D012727:Sex Characteristics; D045165:Testosterone Congeners / Q000378:metabolism
D002352:Carrier Proteins; D004963:Estrenes; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D045165:Testosterone Congeners; C010140:estrophilin; D013196:Dihydrotestosterone; D015741:Metribolone; D004958:Estradiol