TRYPTOPHAN-HYDROXYLASE SYNTHESIS IS INDUCED BY 3',5'-CYCLIC ADENOSINE-MONOPHOSPHATE DURING CIRCADIAN-RHYTHM IN THE RAT PINEAL-GLAND

Tryptophan hydroxylase in the rat pineal gland undergoes diurnal rhythmic activity. Rat pineal glands exhibit increased tryptophan hydroxylase activity when incubated with a cyclic AMP analogue in vitro. Cyclic AMP-dependent protein kinase phosphorylates tryptophan hydroxylase, purified from rat brain, without any modification of its enzyme activity under our experimental conditions. Actinomycin D or cycloheximide decreases the stimulating effect of the cyclic AMP analogue on pineal tryptophan hydroxylase activity. Incubation of pineal glands in the presence of [S-35]methionine showed a cyclic AMP-induced increase in tryptophan hydroxylase synthesis. These results explain the circadian rhythm of tryptophan hydroxylase activity in the rat pineal gland and suggest that the regulation of tryptophan hydroxylase expression by cyclic AMP occurs probably either at the translational level or via transient expression of a transcriptional regulatory element.