We and others have previously demonstrated that tyrosine hydroxylase (TH) gene expression in the adrenal medulla increases with age. The cAMP signal transduction pathway including phosphorylation of the cAMP response element binding protein (P-CREB) are believed to be involved in the gene expression of TH. In vivo administration of forskolin increases both P-CREB and TH mRNA in the adrenal medulla. Cold exposure also increases TH gene expression in young rats. We previously demonstrated that forskolin stimulated adenylyl cyclase activity is elevated in the adrenal medulla with age. We hypothesized that elevated P-CREB may be contributing to the increase in TH gene expression with age and/or the elevated TH gene expression following cold exposure. CREB and P-CREB levels were determined by immunoreactivity in young (6 month) and senescent (26 month) F-344 rats and in young rats with and without cold exposure at 5°C. Basal CREB, levels were diminished by 18% in senescent compared with young rats (64 ±4.3 vs 52 ± 0.7 arbitrary units/mg protein, p=0.039), whereas basal P-CREB levels were 3 fold less in senescent compared with young rats (18 ±2. 1 vs 3.8 ±0.9, p=0.001). With short term cold exposure (5 h) CREB levels were diminished by 37% (63 ±3.7 vs 40 ± 0.7, p=0.004), whereas P-CREB levels decreased nearly 2 fold (24 ±2.8 vs 14 ±1.7). These data do not support the idea that heightened cAMP signal transduction contributes to the increase in TH gene expression with age or following cold exposure, and furthermore, these data indicate that the elevated TH mRNA levels with age and cold exposure are associated with diminished P-CREB levels.
|Number of pages||2|
|Journal||Proceedings of the Western Pharmacology Society|
|State||Published - 1999|