A Comparison of Plasma Protein Changes Induced by Danazol, Pregnancy, and Estrogens*

Abstract

An analysis of 25 plasma proteins was performed on blood drawn from 7 females before and during treatment with danazol. This steroid induced 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 3rd trimester, when the estrogen influence on plasma protein synthesis is most pronounced. Five major types of response were found: albumin and orosomucoid were not influenced by danazol or, after correction for volume expansion, by pregnancy; prealbumin, C.hivin.1-esterase inhibitor and haptoglobins increased substantially during danazol treatment but were not significantly influenced by pregnancy; transferrin, antithrombin III, prothrombin and plasminogen showed marked increases after administration of danazol and during pregnancy; transcortin, ceruloplasmin and .alpha.1-antitrypsin doubled in pregnancy but were not influenced by danazol; and the concentrations of thyroxine-binding globulin, pregnancy zone protein and sex hormone-binding globulin more than doubled in pregnancy and all 3 decreased to 1/3 or less on administration of danazol. The plasma estradiol content fell correspondingly. The different types of plasma protein response found in these 2 groups of patterns fit the hypothesis that hepatocytes contain steroid receptors capable of reacting with estrogens and/or other steroids such as danazol and that they 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.