UP-REGULATION OF BETA(1)-ADRENOCEPTOR MESSENGER-RIBONUCLEIC-ACID IN THE RAT PINEAL-GLAND - NOCTURNALLY, THROUGH A BETA-ADRENOCEPTOR-LINKED MECHANISM, AND IN-VITRO, THROUGH A NOVEL POSTTRANSCRIPTIONAL MECHANISM ACTIVATED BY SPECIFIC PROTEIN-SYNTHESIS INHIBITORS

The uniquely high concentration of beta1-adrenoceptor mRNA (beta1-mRNA) in the pineal gland provides a model for the regulation of GTP-binding protein (G-protein)-linked receptor gene expression within a functioning endocrine gland. By Northern analysis it has been shown that a nocturnal up-regulation of beta1-mRNA in the rat pineal results in a 2.6-fold increase in mRNA levels at the middark phase (2400 h) compared with those at the midlight phase (1200 h). This increase is blocked by administration of the beta-adrenoceptor antagonist propranolol before the onset of darkness. In vitro studies of beta1-mRNA expression in organ-cultured pineals has confirmed beta-adrenoceptor-linked up-regulation of beta1-mRNA. Treatment of cultured pineals with the second messenger drugs forskolin and phorbol 12,13-dibutyrate produced mRNA responses that were again consistent with a primary role of beta-adrenoceptors in the up-regulation of beta1-mRNA. Nuclear runon analysis showed that the acute up-regulation of mRNA was mediated largely through a transcriptional mechanism. An additional novel mode of regulation of beta1-mRNA was also identified; the protein synthesis inhibitors anisomycin and cycloheximide, but not puromycin and emetine, elicited an acute increase in beta1-mRNA in cultured pineals that was not transcriptionally mediated. The mechanism underlying this mode of regulation is discussed with relation to control of the cellular immediate early gene c-fos. The facility to examine both physiological and in vitro changes in beta1-mRNA expression in the pineal will provide further insight into the complexity that is apparent for the molecular regulation of G-protein-coupled receptors.