Somatostatin has been reported to decrease with age in many brain regions and these changes generally have been considered to have important implications for the regulation of both neural activity and neuroendocrine regulatory systems. The purpose of this study was to determine whether the age-related changes in somatostatin concentration in cortex and hypothalamus are attributable to alterations in the regulation of somatostatin gene expression. Hypothalamic and cortical tissue were dissected from young (3-4 month), middle-aged (12-14 month), and old (22 month) male Fischer 344 rats. Total RNA was extracted and dilutions blotted to nitrocellulose. Somatostatin cDNA in expression vector pSP65 was used to produce a 32P-labeled antisense probe for hybridization. After washing, blots were autoradiographed and analyzed by densitometry. Dilutions of total RNA were also probed with 32P-labeled oligo d(pT)16 to determine poly A +RNA levels. Data were expressed as relative somatostatin gene expression (somatostatin mRNA/poly A +RNA). Results indicated that in cortex, relative somatostatin gene expression was similar in young, middle-aged, and old animals (0.54 +/- 0.11, 0.60 +/- 0.08, and 0.51 +/- 0.04, respectively). However, somatostatin gene expression in the hypothalamus decreased consistently with age and ratios in old rats were approximately 50% of levels observed in young animals (p less than 0.05). Northern analysis of RNA revealed a single somatostatin transcript of approximately 0.65 kb in all age groups. In situ hybridization analysis of somatostatin mRNA in the hypothalamus indicated that the age-related decrease in somatostatin gene expression is a consequence of decreased expression within specific hypothalamic nuclei rather than a loss of somatostatin-containing neurons.(ABSTRACT TRUNCATED AT 250 WORDS)