Lj. Zhu et al., Effects of androgen on androgen receptor expression in rat testicular and epididymal cells: A quantitative immunohistochemical study, BIOL REPROD, 63(2), 2000, pp. 368-376
Androgen is essential for maintenance of spermatogenesis in the testis and
for maturation of spermatozoa in the epididymis. The effects of androgen ar
e mediated through its receptor (AR), the levels of which are, in turn, reg
ulated by androgen. Previous studies have shown that AR concentrations in L
eydig and Sertoli cells are differentially regulated during development. Th
e aim of the present study was to determine if cell-type-specific regulatio
n of AR by androgen occurs in testicular and epididymal cells during adulth
ood. Adult male rats were treated with the LHRH-antagonist Azaline B (100 g
/day) by osmotic pump for 1, 2, 3, 4, or 8 wk to suppress endogenous androg
en, with identical numbers of intact control animals at each time period. A
n androgen replacement group was simultaneously treated with the antagonist
and a synthetic androgen, 7 alpha-methyl-19-nortestosterone (MENT), during
the final 4 wk of the experiment. Levels of nuclear AR protein in specific
cell types were quantified by immunohistochemistry in conjunction with com
puter-assisted image analysis. Levels of AR in testicular cells declined sh
arply after treatment with the LHRH antagonist, In Sertoli cells, nuclear A
R levels decreased to 8% of control (P < 0.01) after 4 wk treatment; and to
12% and 17% of control (P < 0.01) in Leydig and myoid cells, respectively.
Androgen replacement resulted in complete recovery of nuclear AR levels in
Sertoli cells (93%, P > 0.05) but in only partial recovery in myoid (69%,
P < 0.01) and Leydig cells (56%, P < 0.01). In the epididymis, tubular epit
helial cells and stromal cells differed in their responses to the LHRH anta
gonist. After 1 wk, nuclear AR levels in caput stromal cells decreased dram
atically to 34% of control (P < 0.01) and in cauda stromal cells to 43% (P
< 0.01). In contrast, the decline of AR levels in epididymal epithelial cel
ls was not as dramatic as that in stromal cells. After 1 wk, the decline in
the caput and cauda was to 87% and 76% of control, respectively. After 8 w
k, nuclear AR levels in stromal cells further declined to 1.1 % in caput an
d 1.4% in cauda, whereas in the epithelial cells, a smaller decline in nucl
ear AR was noted (to 30% in the caput and 45% in the cauda). After androgen
replacement with MENT, nuclear AR levels recovered to more than 90% of con
trol in both epididymal cell types. These results indicate that AR levels i
n the nuclei of adult Sertoli cells depend mainly on the level of androgen,
whereas in the adult Leydig and myoid cells, the androgen dependency is mo
re limited. The results also indicate that in the epididymis, stromal cells
are more sensitive than epithelial cells to the regulation of AR levels by
androgen.