Retinoid receptors involved in the effects of retinoic acid on rat testis development

We have previously shown that retinoic acid (RA) is able to act on the deve lopment of Leydig, Sertoli, and germ cells in the testis in culture (Livera et al., Biol Reprod 2000; 62:1303-1314); To identify which receptors media te these effects, we have now added selective agonists and antagonists of r etinoic acid receptors (RARs) or retinoid X receptors (RXRs) in the same or ganotypic culture system. The RAR cu agonist mimicked most of the effects o f RA on the cultured fetal or neonatal testis, whereas the RAR beta, gamma, and pan RXR agonists did not, The RAR or agonist decreased the testosteron e production, the number of gono-cytes, and the cAMP response to FSH of fet al testis explanted at 14.5 days postconception (dpc). The RAR alpha agonis t disorganized the cords of the 14.5-dpc cultured testis and increased the cord diameter in cultured 3-days-postpartum (dpp) testis in the same way as RA. All these RA effects could be reversed by an RAR alpha antagonist and were unchanged by an RAR beta/gamma antagonist. The RAR beta agonist howeve r, increased Sertoli cell proliferation in the 3-dpp testis in the same way as RA, and this effect was blocked by an RAR beta antagonist. The RAR gamm a and the pan RXR agonists had no selective effect. These results suggest t hat all the effects of RA on development of the fetal and neonatal testis a re mediated via RAR alpha, except for its effect on Sertoli cell proliferat ion, which involves RAR beta.