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

Abstract

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, 5α-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; 5α-DHT induces the same effect. Furthermore, testosterone increases the estradiol output in both germ cell populations whereas 5α-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).

The immunoexpression of androgen receptor, estrogen receptors alpha and beta, vanilloid type 1 receptor and cytochrome p450 aromatase in rats testis chronically treated with letrozole, an aromatase inhibitor

“…The long-lasting lower level of estradiol did not affect the immunolocalization of P450 aromatase in germ cells, however, at the same time, the P450 aromatase immunoreactivity was lower. In vitro studies showed that both testosterone and dihydrotestosterone (DHT) stimulated the expression of the P450arom gene and the aromatase activity in pachytene spermatocytes and round spermatids, while estradiol down-regulated the aromatase transcription in germ cells [41]. Additionally, we detected the presence of P450arom in the cytoplasm of sloughed immature germ cells in the lumen of seminiferous tubules in testes of experimental rats.…”

Aromatase in testis: Expression and role in male reproduction

“…4). In addition, we have shown that androgens and estrogens exert oppsite effects on aromatase gene expression [28,29]. It is noteworthy that the effect of TNF␣ is amplified in presence of dexamethasone (not shown) which is may be supported by the presence of another promoter as shown in adipose tissue [30].…”

“…TGF␤, transforming growth factor beta; TNF␣, tumor necrosis factor alpha; cAMP, cyclic AMP; PS, pachytene spermatocyes and RS, round spermatids. The testicular cells were incubated with these factors then the amount of specific P450arom transcripts and the production of estradiol were determined as described previously [19,28,29].…”

Estrogen synthesis in the hippocampus

“…Gene transcription, resulting from estrogen binding to their cognate receptors, is one way in which local concentrations of estrogens may be regulated (Bourguiba et al 2003;Harada et al 1993;Iivonen et al 2006;Ishunina et al 2007;Roselli et al 1987;Yilmaz et al 2009;Zhao et al 2008). In this context, it is of note that aromatase mRNA may be either downregulated or upregulated in response to estradiol.…”