In vitro data on human hepatoma-culturedcells indicated that insulin-like growth factor 1 (IGF-1) may be a negativeregulator of SHBG synthesis (28).Upon aging, IGF-1 decreases, reducing the inhibitory effect on SHBG production inhepatocytes, which increases SHBG levels (29). This evidence concerns the gene SHBG and hepatocellular carcinoma.