The proposed studies will embrace 2 broad areas of steroid hormone research - metabolism and mechanisms of action. In the former category the following investigations are contemplated: 1) An inquiry into the origin of the extremely high concentrations of estriol-3-sulfate in human breast cyst fluid. Patients awaiting cyst fluid drainage will be given various forms of estriol to see which is taken up most efficiently by the cyst. 2) Cell lines of human breast cancer will be incubated with androstenedione. Specific metabolites, particularly etiocholanolone will be quantified. Metabolism will be assessed in terms of whether the cell line is estrogen-dependent. The studies will be extended to solid tumors obtained at surgery. 3) Profiles of estriol conjugates will be obtained in abnormal pregnant states and comparisons made with normal pregnancy. The area of mechanisms of action will center on the role of proteases in the expression of hormone effects, particularly on the mouse uterus. The effect of the protease inhibitors, antipain and elastatinal on specific enzyme activities such as elastase-like, trypsin-like, peroxidase and ornithine decarboxylase in the mouse uterus will be studied in the perimaturation period. The nature of the elastase-like activity will be studied. Human endometrium obtained at surgery will be analyzed for similar enzyme activities and the concentrations will be related to the endocrine state of the patient.