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Abstract

The effects of androgen on androgen receptor expression in rat testicular and epididymal cells: A quantitative immunohistochemical study (PDF) (HTML) 
Zhu,Li-Ji; Hardy,Matthew P.; Inigo,Ivan V.; Huhtaniemi,Ilpo; Bardin,C.Wayne; Moo-Young,Alfred J.
Biology of Reproduction 63(2): 368-376
Publication date: 2000

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Androgen is essential for maintenance of spermatogenesis inthe testis and for maturation of spermatozoa in the epididymis.The effects of androgen are mediated through its receptor (AR),the levels of which are, in turn, regulated by androgen. Previousstudies have shown that AR concentrations in Leydig and Sertolicells are differentially regulated during development. The aimof the present study was to determine if cell-type-specificregulation of AR by androgen occurs in testicular and epididymalcells during adulthood. Adult male rats were treated with theLHRH-antagonist Azaline B (100 g/day) by osmotic pump for 1,2, 3, 4, or 8 wk to suppress endogenous androgen, with identicalnumbers of intact control animals at each time period. An androgenreplacement group was simultaneously treated with the antagonistand a synthetic androgen, 7-methyl-19-nortestosterone (MENT),during the final 4 wk of the experiment. Levels of nuclear ARprotein in specific cell types were quantified by immunohistochemistryin conjunction with computer-assisted image analysis. Levelsof AR in testicular cells declined sharply after treatment withthe LHRH antagonist. In Sertoli cells, nuclear AR levels decreasedto 8% of control (P < 0.01) after 4 wk treatment; and to12% and 17% of control (P < 0.01) in Leydig and myoid cells,respectively. Androgen replacement resulted in complete recoveryof nuclear AR levels in Sertoli cells (93%, P > 0.05) butin only partial recovery in myoid (69%, P < 0.01) and Leydigcells (56%, P < 0.01). In the epididymis, tubular epithelialcells and stromal cells differed in their responses to the LHRHantagonist. After 1 wk, nuclear AR levels in caput stromal cellsdecreased dramatically to 34% of control (P < 0.01) and incauda stromal cells to 43% (P < 0.01). In contrast, the declineof AR levels in epididymal epithelial cells was not as dramaticas that in stromal cells. After 1 wk, the decline in the caputand cauda was to 87% and 76% of control, respectively. After8 wk, nuclear AR levels in stromal cells further declined to1.1% in caput and 1.4% in cauda, whereas in the epithelial cells,a smaller decline in nuclear AR was noted (to 30% in the caputand 45% in the cauda). After androgen replacement with MENT,nuclear AR levels recovered to more than 90% of control in bothepididymal cell types. These results indicate that AR levelsin the nuclei of adult Sertoli cells depend mainly on the levelof androgen, whereas in the adult Leydig and myoid cells, theandrogen dependency is more limited. The results also indicatethat in the epididymis, stromal cells are more sensitive thanepithelial cells to the regulation of AR levels by androgen.

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