THE INFLUENCE OF INSULIN, BETA-ESTRADIOL, DEXAMETHASONE AND THYROID-HORMONE ON THE SECRETION OF COAGULANT AND ANTICOAGULANT PROTEINS BY HEPG2 CELLS

As a basis for regulatory studies on the influence of hormones on (ant i)coagulant protein production by hepatocytes, we examined the amounts of the plasma proteins antithrombin III (AT III), protein C, protein S, factor II, factor X, fibrinogen, and prealbumin produced by the hep atoma cell line HepG2, into the culture medium, in the absence and pre sence of insulin, beta-estradiol, dexamethasone and thyroid hormone. W ithout hormones these cells produced large amounts of fibrinogen (2,45 2 +/- 501 ng/mg cell protein), AT III (447 +/- 16 ng/mg cell protein) and factor II (464 +/- 31 ng/mg cell protein) and only small amounts o f protein C (50 +/- 7 ng/mg cell protein) and factor X (55 +/- 5 ng/mg cell protein). Thyroid hormone had a slight but significant effect on the enrichment in the culture medium of the anticoagulant protein AT III (1.34-fold) but not on protein C (0.96-fold) and protein S (0.91-f old). This hormone also significantly increased the amounts of the coa gulant proteins factor II (1.28-fold), factor X (1.45-fold) and fibrin ogen (2.17-fold). Insulin had an overall stimulating effect on the amo unts of all the proteins that were investigated. Neither dexamethasone nor beta-estradiol administration did substantially change the amount s of these proteins. We conclude that the HepG2 cell is a useful tool to study the hormonal regulation of the production of (anti)coagulant proteins. We studied the overall process of protein production. i.e., the amounts of proteins produced into the culture medium. Detailed stu dies have to be performed to establish the specific hormonal effects o n the underlying processes, e.g., transcription, translation, cellular processing and transport, and secretion.