What do people mean when they say “AR is upregulated”? Do they mean:
A) The amount of androgen receptors on the surface of cells has been increased
B) The physiological effect induced by a given amount of serum or intracellular androgens has been increased
C) Androgens now have a higher affinity for binding to androgen receptors
D) Some combination of A, B, and C
Something like this :
A) The amount of androgen receptors on the surface of cells has been increased
Except AR is an intracellular receptor. It binds with T or DHT in the cytoplasm, then enters the nucleus of a cell to do the majority of its work.
The Di Loreto study of PFS patients found abnormally high levels of AR protein in certain cell types taken from penile tissue. They antibody-stained the cells to visualize this, so it isn’t just overexpression/upregulation of RNA production that was observed, but an excess of the actual protein. Upregulated AR-RNA production can be inferred from the presence of too much AR protein and fits into the 5ar-i withdrawal hypothesis.
The opposite of this:
B) The physiological effect induced by a given amount of serum or intracellular androgens has been increased