EFFECT OF RETINOID STATUS ON THE MESSENGER-RIBONUCLEIC-ACID EXPRESSION OF NUCLEAR RETINOID RECEPTORS ALPHA-RECEPTOR, BETA-RECEPTOR, AND GAMMA-RECEPTOR, AND RETINOID-X-RECEPTOR ALPHA, BETA, AND GAMMA IN THE MOUSE TESTIS

The testicular gene expression of the retinoic acid receptors, RAR alp ha, -beta, and -gamma, was studied in normal mice and in vitamin A-def icient mice after the administration of all-trans-retinoic acid (ATRA) . All three types of RARs were expressed in normal and/or vitamin A-de ficient testes. Only the expression of RAR beta messenger RNA was tran siently induced within 24 h after ATRA injection. ATRA-induced RAR bet a expression was also found in purified Sertoli cells, suggesting that these cells mediate at least part of the effect of retinoids on germ cells. When an equimolar amount of retinol was administered instead of ATRA. no induction of RAR beta was seen at the point of maximal induc tion by ATRA, suggesting that the effect of retinol was delayed and pr obably less. The related nuclear receptors, RXR alpha, -beta, and, for the first time, gamma, were also shown to be present in the mouse tes tis. Upon administration of ATRA, messenger RNA expression of RXR alph a and -beta did not change significantly. The expression of RXR gamma was too low to allow quantification. Finally, the effect of the retino id metabolism inhibitor liarozole on ATRA-induced proliferation of A s permatogonia was examined. The labeling index of A spermatogonia, 24 h after the administration of 0.25 mg ATRA, was significantly lowered b y liarozole due to a shift of the maximal 5-bromo-deoxyuridine incorpo ration to an earlier point (20 h). This indicates that liarozole delay s retinoid metabolism, thereby increasing the actual ATRA concentratio n, and more importantly, that ATRA by itself is an active retinoid in spermatogenesis. Apparently, ATRA does not need to Ire metabolized to 4-oxo-RA, which was previously shown to be a more potent inducer of sp ermatogonial proliferation than ATRA, to be effective.