Androgen metabolism and biotransformation in nontumoral and malignant human liver tissues and cells

Sex Differences: A Resultant of an Evolutionary Pressure?

“…As it is known that in females estrogens directly regulate large part of the genes above mentioned, the differential expression reported may be explained by the fact that, contrary to females, males have low circulating levels of estrogens, in the liver do not expressed the enzyme synthesizing estrogens from testosterone (aromatase) (Granata et al, 2009;Harada et al, 1993), and have an hepatic content of ER protein 3-5 fold lower than females (Della Torre et al, 2016). In mammals, however, other mechanisms regulating liver functions were established with evolution; first of all, the brain is sexually differentiated by the activity of male gonads in a window of time that occurs around birth.…”

Dehydroepiandrosterone-induces miR-21 transcription in HepG2 cells through estrogen receptor β and androgen receptor

“…1A). DHEA is converted to AR ligands (Granata et al, 2009; Green et al, 2012; Mo et al, 2006; Provost et al, 2000; Rege and Rainey 2012; Rijk et al, 2012; Vollmer et al, 2012), directly activates AR in mouse brain and recombinant AR in vitro (Lu et al, 2003), and directly activates mutant ARs in prostate cancer (Mizokami et al, 2004; Tan et al, 1997). Thus, we evaluated the roles of ERα, ERβ, and AR in regulating pri-miR-21 and mature miR-21 expression in HepG2 cells.…”

“…Here we demonstrated that DHEA increased pri-miR-21 transcription in HepG2 cells and in mouse liver, demonstrating in vivo activation of miR-21 expression by DHEA. The physiological relevance of this study is that the human liver is a major site for metabolism, conjugation, and catabolism of steroids mediated by key enzymes including 17β-HSD, 5α-reductase, and aromatase (Granata et al, 2009). DHEA is converted to higher affinity androgens and estrogens (Fig.…”

“…6A) depending on tissue- and cell- specific expression of metabolizing enzymes (Labrie 2010; Labrie et al, 2005; Traish et al, 2011). HepG2 cells express aromatase, 17β-HSD, 5α- and 5β-reductases, and 3β-HSD (Granata et al, 2009). The gender disparity and role of sex steroids in hepatocellular cancer have been reviewed, implicating active AR in augmenting HCC risk (Yeh and Chen 2010) whereas E 2 suppression of IL-6 lowers HCC risk in females (Dorak and Karpuzoglu 2012).…”

Merlin, the product of NF2 gene, is associated with aromatase expression and estrogen formation in human liver tissues and liver cancer cells

“…Both methodological approaches and technical procedures used to inspect rates and patterns of sex steroid metabolism, either in vivo or in vitro, have been developed, optimized and implemented in our laboratories, as extensively described elsewhere [17]. …”