Age-related alterations in the catecholamine-sensitive adenylate cyclase system of the prostate

Considerably reduced responses to stimulation by isoproterenol of adenylate cyclase activity of prostatic membranes were observed in 12- to 18-month-old rats, compared to 3-month-old animals. Plasma testosterone levels were significantly lower in 18-month-old rats, while 12-month-old animals showed levels similar to those present in young ones. A decrease in isoproterenol activation of adenylate cyclase was not associated with a fall in beta-adrenergic receptor sites. Guanine triphosphate and 5'-guanylylimidodiphosphate (Gpp(NH)p) were effective in potentiation of isoproterenol activation of adenylate cyclase and altering the affinity of beta-adrenergic receptors for the agonist in membranes from young rats but not from the aged. The age-induced refractoriness to isoproterenol or Gpp(NH)p was observed without a significant loss in NaF-stimulated activity. Prior incubation of aged membranes with isoproterenol and GMP restored subsequent stimulation by Gpp(NH)p, presumably due to the clearance of inhibitory GDP tightly bound to the guanine nucleotide regulatory components in aged membranes. These results indicate that the dysfunction in the adenylate cyclase system of old prostates may not be related to a modification in the beta-adrenergic receptor per se, but to, in part, a defect in the interaction of activating guanine nucleotides with regulatory components of the adenylate cyclase system.