Androgen receptor distribution in rat testis: new implications for androgen regulation of spermatogenesis.

Abstract

The distribution of the androgen receptor (AR) in the adult rat testis was determined by biotin-streptavidin immunoperoxidase, employing tissue embedded in polyester wax which preserves antigenicity without compromising tissue preservation. The antibody probe used, which has been characterized previously, was an affinity purified, rabbit polyclonal antibody raised to the amino terminus peptide of the rat AR. Within the interstitial compartment, AR immunostaining was detected in some Leydig cells and all smooth muscle cells forming the walls of blood vessels, but endothelial cells of blood vessels were negative. Furthermore, in those Leydig cells that were clearly identified as exhibiting AR immunostaining, the intensity of the reaction varied. In the seminiferous tubules AR immunostaining was observed in all peritubular myoid cell nuclei, but not in the distal layer of lymphatic endothelial cells. In Sertoli cells, nuclear AR immunostaining was stage specific. Moderate AR immunostaining first became evident at late stage IV or early stage V of the cycle, reached a robust peak at stages VII-VIII, and then disappeared completely. Specific AR immunostaining was also discerned in the nuclei of stage XI elongated spermatids, the spermatids in which nuclear elongation is apparent but chromatin condensation has not yet begun. Next, with onset of chromatin condensation, nuclear AR immunostaining in elongated spermatids was not discerned concomitant with its detection in the cytoplasm of the germ cells. These results are interpreted in the following manner: 1) The presence of AR in Leydig cells is consistent with the hypothesis that androgens modify Leydig cell activity in an autocrine fashion. Further, that not all Leydig cells exhibited AR immunostaining at steady state suggests a differential, functional activity of these cells within the population. 2) The intense AR immunostaining of smooth muscle cells present in the interstitium indicates that these cells are targets for androgens. 3) AR immunoreactivity in both Sertoli and peritubular myoid cells suggests their involvement in the androgenic control of spermatogenesis. The stage specific AR immunoreactivity in Sertoli cells, however, may be more indicative of a specific androgen response during these stages, whereas peritubular cells may participate in the tonal maintenance of spermatogenesis. 4) The specific presence of AR in step 11 elongated spermatids may suggest that androgens can act directly on germ cells to regulate spermatogenesis.

Neonatal Gonocyte Differentiation in Mongolian GerbilMeriones unguiculatusInvolves Asynchronous Maturation of Seminiferous Cords and Rapid Formation of Transitional Cell Stage

“…Strong AR immunoreactivity was also observed in interstitial cells already on the first postnatal day and in Sertoli cells from 21 d onward, parallel to findings in other rodents (Kimura et al, 1993;Bremner et al, 1994;Zhou et al, 1996). The lack of AR immunoreaction for spermatogonial subtypes is also consistent with previous reports (Bremner et al, 1994;Vornberger et al, 1994;Matsumiya et al, 1999). AR functions as a ligand-dependent transcription factor, since ligand binding is a prerequisite for its transport to the nucleus where it accesses and regulates an array of androgen-responsive genes (Georget et al, 1997;Wang et al, 2009).…”

Cell-specific and Hormone-regulated Expression of Gonadotropin-regulated Testicular RNA Helicase Gene (GRTH/Ddx25) Resulting from Alternative Utilization of Translation Initiation Codons in the Rat Testis

“…The action of androgen on GRTH protein expression in germ cells appears to be cell-specific, although germinal cells do not exhibit either gonadotropin or androgen binding activity (16,17). In contrast to the up-regulation of GRTH gene expression caused by hCG-induced androgen action in the Leydig cells, GRTH protein levels in purified pachytene spermatocytes were not affected by hormonal stimulation.…”

Oligozoospermia with normal fertility in male mice lacking the androgen receptor in testis peritubular myoid cells

“…The interactions between PM cells and Sertoli cells provide an example of a mesenchymal-epithelial cell interaction (1). PM cells contain a high percentage of the androgen receptor (AR) (2,3) and provide a site for androgen signaling. It has been reported that the PM cells can synthesize several secretory products.…”

“…The local actions of androgen on testis functions were initially demonstrated when testosterone alone, in the absence of the gonadotropins, leuteinizing hormone (LH), and follicle-stimulating hormone (FSH), could support spermatogenesis (11). Furthermore, AR has been detected in Sertoli, Leydig, PM, and spermatid cells (round and elongated) (2,3), and mice lacking functional AR develop testicular feminization syndrome (12). Previously, we have shown that Sertoli cellspecific AR Ϫ/y mice revealed incomplete germ cell development and lowered serum testosterone levels, which resulted in azoospermia and infertility (13).…”