The long-term objective of the proposed research is a better understanding of the molecular mechanism of hormonal regulation of specific protein synthesis in the liver and of changes in hormone responsiveness of the hepatic tissue during development and aging. This two-fold objective will be pursued through the Alpha2u globulin model system. Hormonal regulation of Alpha2u globulin in rat liver will be investigated in the whole animal, in cultured hepatocytes and in heterologous cells transfected with the cloned Alpha2u globulin gene. Special emphasis will be placed on the role of hormone receptors and are organization of the nuclear substructures in the alteration of hormone responsiveness during aging. The coordinate synthesis of the androgen-inducible Alpha2u globulin and androgen-repressible 26 kilodalton hepatic protein (LP-26) will serve as markers for changing androgen sensitivity of hepatocytes. In order to explore the possible role of the cytoplasmic androgen binding (CAB) protein in the regulation of Alpha2u globulin and LP-26, monoclonal antibody to CAB will be prepared after partial purification of this protein from the male rat liver cytosol. Finally, the proposed research will attempt to elucidate the interaction between androgen, glucocorticoids, growth hormone and insulin in the regulation of Alpha2u globulin. Results obtained through this investigation are expected to provide significant information that will enhance our understanding of the mechanism of hormone action relevant to management of endocrinopathies such as diabetes, hypothyroidism and endocrine disorders during development, muturation and aging.
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