Effects of androgen on androgen receptor expression in rat testicular and epididymal cells: A quantitative immunohistochemical study

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.