Esistono due forme di recettori androgeni : uno a forma di A ed uno a forma di B. Il Dott. Sawaya e la Dottoressa Maria Hordinsky hanno scoperto che la forma dei recettori cambia con il trattamento con finasteride da A a B.
La forma B promuove la crescita normale ed è predominante nella zona posteriore della testa, ove i capelli non vengono colpiti da calvizie androgenetica.
Functional activities of the A and B forms of the human androgen receptor in response to androgen receptor agonists and antagonists.
Mol Endocrinol 1998 May;12(5):654-63 (ISSN:
0888-8809)
Gao T; McPhaul MJ Department of Internal Medicine, The University of Texas
Southwestern Medical Center, Dallas 75235, USA.
The androgen receptor (AR) is present in many cells in two forms. The B form migrates with
an apparent mass of 110 kDa and constitutes more than 80% of the immunoreactive
receptor in most cell types. The A form of the AR migrates with an apparent mass of
87 kDa, appears to derive from internal translation initiation at methionine-188 in
the AR open-reading frame, and usually constitutes 20% or less of the immunoreactive
AR present. Previous experiments designed to examine the functional capacity of the
A and B forms of the AR have been hampered by marked differences in the expression
levels of the two isoforms, as the nucleotide sequence surrounding the codon encoding
methionine-188 causes it to be used inefficiently as a translation initiation site.
To circumvent this, we altered the nucleotide sequence surrounding methionine-188 to
render it more similar to that surrounding the codon encoding methionine-1.
Transfection of a cDNA containing these changes resulted in similar levels of
expression of A and B forms of the AR as assessed by immunoblot
assays using antibodies directed at an epitope preserved in both. Functional activities of
these cDNAs were assessed using cotransfection assays that employed two model
androgen-responsive genes (MMTV-luciferase and PRE2-tk-luciferase) in response to
mibolerone, a potent androgen agonist, in three different cell lines. These studies
demonstrated subtle differences in the activities of the A and B isoforms, which
depended on the promoter and cell context. Additional studies failed to reveal any
major differences in the responses of the AR-A and AR-B isoforms to a variety of androgen
agonists and antagonists, suggesting that the previously reported functional defect
of the AR-A is due principally to its level of expression. When assays of AR
function are performed under conditions in which levels of expression of the two
isoforms are equivalent, the AR-A and AR-B possess similar functional activities.