Steroids control the aromatase gene expression in purified germ cells from the adult male rat

The ability of the testis to convert irreversibly androgens into estrogens is related to the presence of a microsomal enzymatic complex named aromatase. In rodents, germ cell production of estrogens is known, although the regulation of the cytochrome P450 aromatase (P450 arom) gene expression is not completely elucidated. In the present study, we have investigated the putative effects of steroids (testosterone, 5alpha-dihydrotestosterone (DHT) and estradiol) on Cyp19 gene expression in purified adult rat pachytene spermatocytes (PSs) and round spermatids (RSs). Using a highly specific quantitative competitive RT-PCR method we established that testosterone enhances in a dose- and time-related manner aromatase gene expression in PSs and RSs; 5alpha-DHT induces the same effect. Furthermore, testosterone increases the estradiol output in both germ cell populations whereas 5alpha-DHT was inefficient, therefore suggesting that the effect of androgens on P450 arom gene transcription was independent of estrogen formation. In fact estradiol inhibits the Cyp19 gene expression in PSs and RSs. ICI 182780, an estrogen receptor antagonist, has no effect on testosterone-stimulated aromatase expression in PSs and RSs. By contrast, ICI 182,780 suppresses the inhibitory effect of estradiol on P450 arom mRNA expression in PSs and RSs. Similarly, nilutamide, a non-steroidal anti-androgen specific for androgen receptors, abolishes the testosterone-stimulated aromatase expression in PSs and RSs. These observations show that androgens up-regulate aromatase gene expression in purified adult rat germ cells whereas estrogens exert an opposite effect, which may suggest the presence of androgen and estrogen responsive elements on the aromatase promoter(s).