Altered androgen metabolism eventually leads hepatocellular carcinoma to an impaired hormone responsiveness.
Sex steroid hormones are thought, among several other risk factors, to play a role in liver malignancies. For example, from epidemiological studies in hepatocellular carcinoma (HCC), a clear disadvantage for male sex is evident. In addition, elevated levels of serum testosterone (T) and increased T to Estradiol (E(2)) ratio have been reported to predict an increased risk of HCC for male cirrhotic patients. On the other hand, palliative treatment of liver cancer patients with anti-hormones has been widely used in the past. However, the molecular mechanism(s) underlying sex steroid action on either normal or transformed liver cells, have not yet been fully clarified, nor endocrine discriminants have been satisfactorily assessed for an adequate characterization of liver cancer tissues. In this paper, we report studies on hormonal status of human liver tissues and cells, especially focusing on androgens, to better define endocrine end-points of interest for HCC. A consistent evidence from ex vivo or in vitro systems strongly suggests that high affinity binding sites of androgens are expressed at sufficient concentrations to induce a biological response in either normal or phenotipically transformed hepatocytes; in the latter, however, high heterogeneity and/or more scattering concentrations were encountered. Further, experimental data seem to suggest that lack of response to androgens may be due to a rapid metabolic conversion of steroids by neoplastic tissues and cells. Cancer hepatocytes privilege in fact 5beta more than 5alpha metabolic pathway of androgens. This may eventually lead biologically active androgens to be transformed into less active derivatives, as it occurs for T which is massively converted (>90% at 6 h) thus hindering the whole mechanism of action of androgens.
Granata
Orazia M
OM
Unit of Experimental Oncology & Palermo Branch of IST-Genoa, Department of Clinical Oncology, M. Ascoli Cancer Hospital Center, ARNAS., Civico, Palermo, Italy.
Carruba
Giuseppe
G
Montalto
Giuseppe
G
Miele
Monica
M
Bellavia
Vincenzo
V
Modica
Giuseppe
G
Blomquist
Charles H
CH
Castagnetta
Luigi A M
LA
D000728:Androgens / Q000378:metabolism* / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D012739:Gonadal Steroid Hormones / Q000378:metabolism / Q000494:pharmacology; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology; D011849:Radioactive Tracers; D011944:Receptors, Androgen / Q000032:analysis / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000728:Androgens; D012739:Gonadal Steroid Hormones; D011849:Radioactive Tracers; D011944:Receptors, Androgen; D013739:Testosterone