Effects of the antileukemic drug L-asparaginase on sex hormone-binding globulin: studies in vivo and in vitro

L-asparaginase, an antineoplastic drug used in the treatment of acute lymphoblastic leukemia (ALL), has been previously shown to inhibit the hepatic synthesis of thyroxine-binding globulin (TBG). In two children treated by this drug for ALL, a dramatic decrease in serum sex hormone-binding globulin (SHBG) concentrations was also observed. Serum SHBG levels were still below normal 10 days after L-asparaginase withdrawal. To ascertain whether this reduction was due to the inhibition of SHBG synthesis, SHBG was measured by an immunoradiometric assay (IRMA) in the medium from human hepatoblastoma-de-rived cells, Hep G2 cells, grown in the absence or presence of graded amounts of the drug from 0.1 nM to 0.1 mM. The results showed a dose-dependent inhibition of SHBG synthesis, with a 50% reduction of SHBG in the medium, assayed by IRMA, using 250 nM L-asparaginase. Furthermore, a time-dependent inhibition was observed using a fixed concentration of the drug (50 nM) added for variable time intervals (1–4 days). These data suggest that the changes observed in vivo are likely due to the inhibitory effect exerted by the drug on SHBG synthesis. This action is not specific, but is part of a general effect at the hepatic level.