A comparison of plasma protein changes induced by danazol, pregnancy, and estrogens

Analysis of 25 plasma proteins was performed on blood drawn from 7 females before and during treatment with danazol. This steroid was found to induce a pattern of plasma protein changes similar to but not identical with that of other 17 alpha-alkylated anabolic steroids. For comparison, the same 25 plasma proteins were analyzed in blood from pregnant women in their third trimester, when the estrogen influence on plasma protein synthesis is most pronounced. Five major types of response were found. 1) Albumin and orosomucoid were not influenced by danazol or, after correction for volume expansion, by pregnancy. 2) Prealbumin, C1-esterase inhibitor, and haptoglobins increased substantially during danazol treatment but were not significantly influenced by pregnancy. 3) Transferrin, antithrombin III, prothrombin, and plasminogen showed marked increases after administration of danazol and during pregnancy. 4) Transcortin, ceruloplasmin, and alpha 1-antitrypsin doubled in pregnancy but were not influenced by danazol. 5) The concentrations of T4-binding globulin, pregnancy zone protein, and sex hormone-binding globulin more than doubled in pregnancy, and all three decreased to one third or less on administration of danazol. The plasma estradiol content fell correspondingly. The different types of plasma protein response found in these two groups of patients fit the hypothesis that hepatocytes contain steroid receptors capable of reacting with estrogens and/or other steroids such as danazol and, thus, influence the biosynthetic rate of many but not all plasma proteins according to a specific pattern. The synthesis of some of the estrogen-sensitive proteins is depressed after intake of danazol, which suggests that there is a competition for the receptors in the hepatocytes as there is for other estrogen target tissues.