INTRACELLULAR PARTITIONING OF ANDROGEN RECEPTOR IMMUNOREACTIVITY IN THE BRAIN OF THE MALE SYRIAN-HAMSTER - EFFECTS OF CASTRATION AND STEROID REPLACEMENT

The effect of castration and steroid replacement on the intracellular partitioning of the androgen receptor in the brain of the male Syrian hamster was determined using immunocytochemistry. Androgen receptors w ere visualized using the PG-21 antibody (G. S. Prins) on 40-mum corona l brain sections from hamsters perfused with 4% paraformaldehyde with or without 0.4% glutaraldehyde. Control studies confirmed antibody spe cificity in gonad-intact and castrate males. In the normal adult male, androgen receptor immunocytochemistry reveals intense staining confin ed to the cell nucleus. Castration caused a gradual increase in cytopl asmic labelling within 2 weeks, accompanied by a reduction in nuclear staining intensity in androgen receptor-containing neurons throughout the brain. Cytoplasmic androgen receptor staining was eliminated after treatment of orchidectomized males for only 8 h with exogenous testos terone. Likewise, long-term exposure to testosterone and dihydrotestos terone, a nonaromatizable androgen, maintained nuclear androgen recept or immunoreactivity. However, exposure to low physiologic concentratio ns of estrogen was not effective in this regard. In addition, we deter mined that nuclear androgen receptor immunoreactivity decreases in res ponse to inhibitory short-day photoperiod, but without an increase in cytoplasmic immunostaining. This appears to be due to the decrease in androgen production by the testis, rather than a direct photoperiodic effect, because testosterone supplementation to short-day males restor ed the intensity of nuclear androgen receptor immunoreactivity to leve ls comparable to those in the intact male. These findings are compatib le with a new model for the intracellular localization of androgen rec eptors, in which a subset of unoccupied receptors is located in the ce ll cytoplasm in the absence of ligand. They further demonstrate the re partitioning of such cytoplasmic receptors, thereby confirming and ext ending previous observations using biochemical techniques on the regul ation of neuronal androgen receptors.