Testosterone reverses a senescent decline in extrahypothalamic vasopressin mRNA

The biosynthetic activity of extra-hypothalamic vasopressin (VP) neurons in the bed nucleus of the stria terminalis (BNST) is regulated by gonadal steroids. These neurons have also been implicated in a number of behaviors that are impaired in aging. We previously reported that VP mRNA labelling in the BNST is decreased in senescent rats. We hypothesized that the age-related decrease in VP mRNA labelling is due to the decline in circulating testosterone (T) levels in aged animals. T or saline was administered peripherally for 1 month in physiologic or superphysiologic doses to 3 month old or 24 month old Fischer 344 male rats. In situ hybridization and quantitative autoradiography for VP mRNA in the BNST were performed using a 48-base ³⁵S-labelled oligonucleotide probe. Administration of T completely reversed the decline in VP mRNA labelling in the aged animals. Superphysiologic T further increased VP gene expression in both age groups. These data are consistent with a previous report of T-induced increase in VP immunoreactive fiber density in other extrahypothalamic regions of the brain in aged rats. This study offers further evidence that alterations in the hormonal milieu may play an important role in modulating neuronal biosynthetic activity in senescence.