With degenerated dark cells free in the lumen of seminiferous tubules. This histological effect could be associated with the observed down-regulation of RGN gene XAV939 284028-89-3 expression in testis. Indeed, androgens are regulators of testicular cell death and considered as germ cell survival factors. The in silico analysis of the RGN promoter region revealed different androgen response elements upstream from the transcription initiation site. Moreover, the RGN-mediated regulation of apoptosis has been demonstrated in vivo and in vitro. RGN inhibits apoptosis through the up-regulation of Akt-1 and Bcl-2 expression and the down-regulation of caspase-3 expression. The anti-apoptotic effect of RGN has been demonstrated using knockout mice, whose cells are more prone to apoptosis than their wild-type counterparts. The reduction of RGN expression via androgen administration could inhibit normal spermatogenesis through the stimulation of abnormal apoptosis and the termination of germ cell line maturation. RGN expression is modulated through estrogen hormones. The regulation of RGN expression through estrogens was first described in 1995 in the liver of rats receiving the subcutaneous administration of 17b-estradiol, resulting in an increase in RGN mRNA expression. Conversely, the administration of 17b-estradiol reduced RGN expression in the kidney cortex of rats. More recently, the effect of sex steroid hormones on RGN expression in the breast and prostate has been demonstrated. The administration of 17b-estradiol to rats induced the down-regulation of RGN expression in the prostate and mammary gland. Consistent with these findings, we observed that the estrogen administration significantly decreased RGN expression not only in the prostate but also in the testis and bulbo-urethral glands. In particular, the estrogen administration caused a decrease of RGN expression in bulbo-urethral glands of veal calves, but not in beef cattle. This marked difference is likely due to physiological levels of the sex steroid hormones in adult male animals, as previously described for the expression of other estrogen-controlled genes. Moreover, the different treatment schedule could influence the RGN expression. It has been suggested that RGN has a physiological function in the prostate, as the expression of this protein is down-regulated in prostate cancer tissues, and RGN immunoreactivity is correlated with the grade of adenocarcinoma cellular differentiation. Conversely, RGN expression and the estrogen-mediated down-regulation of this protein in the bulbo-urethral glands are reported for the first time in the present study. However, further studies are required to determine the precise RGN function in these organs. The effect of 17b-estradiol on morphology of the prostate and bulbo-urethral glands was confirmed by typical hyperplasia and metaplastic lesions observed in treated veal calves. The effect of sex steroid hormones on RGN gene expression could play an important role in the indirect identification of animals illegally treated with hormones to improve the safety of meat production. This “omics” technology is based on the concept that after the identification of a specific transcription.