MESSENGER-RIBONUCLEIC-ACID OF RAT TESTICULAR RETINOIC ACID RECEPTORS - DEVELOPMENTAL PATTERN, CELLULAR-DISTRIBUTION, AND TESTOSTERONE EFFECT

In order to understand the physiological importance and molecular mech anisms of retinoic acid regulation of spermatogenesis, we examined the ontogeny of the steady-state level of the mRNAs of retinoic acid rece ptor (RAR) alpha and gamma in testes; we also used Northern blot cDNA hybridization to examine the distribution of RAR alpha and RAR gamma i n spermatogenic cells isolated from 60-day-old rats. In addition, we i nvestigated the effects of exogenous testosterone on the steady-state levels of mRNA of RAR alpha and gamma in testes of 20-day-old rats. Th e steady-state levels of both the 3.4- and 2.7-kb mRNA transcripts of RAR alpha in rat testes remained relatively unchanged until 20-21 days of age, then declined thereafter. Comparison of the relative abundanc e of the RAR alpha transcripts in Sertoli cells isolated h om 20-day-o ld rats with that found in mixed spermatogenic cells isolated from 40- day-old rats suggests that both the 3.4- and the 2.7-kb transcripts we re expressed more abundantly in Sertoli cells. Whereas young and pachy tene spermatocytes, as well as young and elongated spermatids, all con tained the 3.4-kb transcript of RAR alpha, only trace amounts of the 2 .7-kb transcript was detected in spermatogenic cells. In addition, tra ce amounts of a smaller transcript of RAR alpha (1.8 kb) was detected in both Sertoli cells and spermatogenic cells, and two larger transcri pts (4.0 and 7.0 kb) were detected exclusively in spermatogenic cells. In contrast, a single 3.4-kb mRNA transcript of RAR gamma was detecte d in rat testes. The steady-state level of this mRNA transcript steadi ly increased and reached a maximum by 20 days of age, then decreased t hereafter. Whereas Sertoli cells and spermatocytes contained relativel y high levels of the 3.4-kb transcript of RAR gamma, trace amounts of this transcript were also detected in spermatids. In addition, a small er mRNA transcript (2.0 kb) of RAR gamma was detected exclusively in p achytene spermatocytes. Administration of exogenous testosterone to 20 -day-old rats resulted in a time- and dose-dependent increase of both the 3.4-and 2.7-kb transcripts of RAR alpha, but a decrease in the 3.4 -kb transcript of RAR gamma. These observations demonstrate that both Sertoli cells and germ cells are capable of expressing different retin oic acid receptors. It is postulated that retinoic acid may regulate t he differentiation of spermatogenic cells either directly or through i ts actions on Sertoli cells. Furthermore, the differential effects of testosterone on the steady-state levels of mRNA of testicular RAR alph a and gamma suggest that an RAR-mediated mechanism may be involved in the testosterone regulation of some Sertoli cell functions.