This application describes new investigational activities which are based upon the results of studies prrformed in previous years of this program. The new studies will examine five androgen regulated components of rat prostate metabolism: prostatic androgen receptors, L-ornithine decarboxylase (ODC), S-adenosyl-L-methionine decarboxylase (AMDC), secretory acid phosphatase (APase), and androgen metabolism, which we have established to be specifically diminished during aging. We will examine, at the molecular level, possible causes of these alterations in order to determine if they are the consequence of aging-altered post-translational events: enhanced protein degradation, aging-associated production of altered enzymes, altered inductive responses to androgen; or are indicated to be the result of aging-altered primary gene function. Monospecific antibodies will be prepared against highly purified rat ODC, AMDC, and APase in order to perform quantitative determinations of enzyme mass by radioimmunoassay, to measure rates of protein synthesis by immunoprecipitation of radiolabeled proteins, and for immunofluorescent identification of testosterone responsive cells. Protein degradation will be quantitated by measurement of enzyme or androgen receptor half-life. Aging-associated production of altered enzymes will be assessed by studies of heat inactivation and by quantitation of specific activity and activity per unit antigen. Altered inductive responses will be assessed by acute hormone treatment to establish temporal relationships, and by chronic treatment to assess trophic responses. Selected morphometric characterization of prostatic tissues will be performed. The studies will use young mature (3 to 4-month-old) and aged (24 to 26-month-old) inbred AXC rats.
