Androgen modulation of the messenger ribonucleic acid of retinoic acid receptors in the prostate, seminal vesicles, and kidney in the rat.

Abstract

Previously, we reported that the steady state level of messenger RNA (mRNA) transcripts of retinoic acid receptors (RAR) alpha and gamma in the testes of 20-day-old rats can be modulated by exogenous testosterone. These results suggest that androgen regulation of Sertoli cell functions may involve biochemical events mediated by RAR genes. In this study, we examined the effects of castration and testosterone replacement on the steady state level of mRNA transcripts for RAR alpha and gamma in the prostate, seminal vesicles, and kidney of the rat. Northern blot analysis revealed that in intact adult rats, the relative steady state levels of the 3.4- and 2.7-kilobase (kb) mRNA transcripts for RAR alpha and the 3.4-kb transcript for RAR gamma in the prostate were at least 20-fold higher than those in the seminal vesicles and kidney. The relatively high abundance of RAR mRNA transcripts in the prostate suggests the physiological importance of RAR-mediated processes in this organ. Castration resulted in an increase in the level of RAR mRNA transcripts in the prostate and seminal vesicles, reaching a maximum of 2- to 4-fold in the prostate and 15- to 23-fold in the seminal vesicles within 6 days. On the other hand, the levels of mRNA transcripts of RAR alpha and -gamma in the kidney were reduced by 40-50% 1 day after castration. The effects of castration on RAR mRNA levels in all three organs were prevented by implantation of 3-cm testosterone capsules at the time of castration, a regimen that provides physiological levels of serum testosterone. In a subsequent experiment, adult male rats were given a single sc injection of 2 mg testosterone 3 days after castration. This treatment resulted in an acute suppression of the level of RAR mRNA transcripts in all three organs within 30 min. Thereafter, the levels of RAR alpha and -gamma mRNA transcripts in the prostate continued to decrease, whereas those in the seminal vesicles returned to the castrated levels within 6 h. On the other hand, RAR mRNA levels in the kidney rebounded by 1 h and remained at the level found in the untreated castrated rats. These results demonstrate that the steady state level of mRNA transcripts for RAR alpha and -gamma in the prostate, seminal vesicles, and kidney can be modulated by testosterone in organ-specific manners, thus suggesting that the RAR-mediated processes may be involved in the effects of androgen in these organs. Furthermore, the relatively low increment in prostatic RAR mRNA levels after castration compared to that in the seminal vesicles demonstrates a difference in androgen responses between these two organs. This difference could dictate the efficacy of the effects of androgen on cellular function and may contribute to the disparate vulnerabilities to androgen-related uncontrolled cell proliferation and/or malignancy in the prostate and seminal vesicles.