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

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 ab out the signal transduction pathways leading to the activation of pfc1, inc reased ptc1 transcription has always been associated with elevated HH activ ity and decreased activity of cAMP-dependent protein kinase A. Here, we dem onstrate that in the mammalian pineal gland, ptc1 expression exhibits a dra matic diurnal rhythm with peak expression at midnight. ptc1 mRNA expression in the pineal is regulated by a clock mechanism mediated by the superior c ervical ganglion. Most importantly, ptc1 transcription can be induced by ag ents activating the cAMP signal transduction pathway both in vivo and in vi tro and appears to be independent of HH signaling.