Circadian rhythm of patched1 transcription in the pineal regulated by adrenergic stimulation and cAMP

Abstract

The tumor suppressor patched1 (PTC1), a product of the mammalian homologue of the Drosophila segment polarity gene patched, is a receptor for hedgehog (HH) and is crucial for embryonic development. Although little is known about the signal transduction pathways leading to the activation of ptc1, increased ptc1 transcription has always been associated with elevated HH activity and decreased activity of cAMP-dependent protein kinase A. Here, we demonstrate that in the mammalian pineal gland, ptc1 expression exhibits a dramatic diurnal rhythm with peak expression at midnight, ptc1 mRNA expression in the pineal is regulated by a clock mechanism mediated by the superior cervical ganglion. Most importantly, ptc1 transcription can be induced by agents activating the cAMP signal transduction pathway both in vivo and in vitro and appears to be independent of HH signaling.