Photoneural regulation of rat pineal hydroxyindole-O-methyltransferase (HIOMT) messenger ribonucleic acid expression: An analysis of its complex relationship with HIOMT activity

In the pineal gland, synthesis of melatonin requires O-methylation catalyze d by hydroxyindole-O-methyltransferase (HIQMT; EC 2.1.1.4). We investigated in vivo the molecular mechanisms involved in the regulation of rat pineal HIOMT messenger RNA (mRNA) expression and activity using in situ hybridizat ion and radioenzymatic assay. HIOMT mRNA levels and activity are both detec table during the daytime and display nocturnal increases of 100% and 30%, r espectively. These variations are controlled by the endogenous clock, as th ey persist in constant darkness. The nocturnal increase in HIOMT mRNA mainl y results from a beta(1)-adrenergic stimulation of HIOMT gene expression wi thout requiring de novo synthesis of a transcription factor. In contrast, t he nocturnal increase in HIOMT activity appears independent of beta(1)alpha (1)-adrenergic stimulation. A light pulse at night abolishes the nighttime increase in HIOMT mRNA, but not HIOMT activity. Constant light application for up to 11 days does not depress HIOMT mRNA levels lower than the daytime levels, but decreases enzyme activity down to 50% of the daytime level. Th is finding indicates that the nocturnal stimulation of HIOMT gene expressio n is required for sustaining a basal level of activity over a few days. Our data suggest 1) that HIOMT gene expression is partly regulated by beta(1)- stimulation; and 2) that HIOMT activity is regulated over the short term by a nonnoradrenergic stimulus and over the long term by noradrenergic stimul ation.