Ontogeny of the pineal response to norepinephrine

The Syrian hamster pineal displays age‐dependent changes in melatonin output measured in vitro. Between the ages of 4 and 19 days, pineal melatonin generation in response to 10 μM norepinephrine (NE) increased 34‐fold. Production of melatonin by cultured pineals from 1‐week‐old hamsters showed a clear dose responsiveness to NE: The most effective dose was 10 μM and the response declined at both higher and lower doses. When cultured pineals from 7‐day‐old animals were exposed to four cycles of NE in the medium (10 hr 10 μM NE: 14 hr 0 M NE), the melatonin output followed the driving rhythm with a rising lag time of 8 hr and a falling lag of 4 hr. This time course is consistent with the conclusion [Santana et al., 1990; Gonzalez‐Brito et al., 1990] that transcription events lead to a long lag time between the stimulus and the onset of melatonin synthesis. In the absence of exogenous NE, melatonin output from most glands dropped to undetectable levels in just over 2 days; however, even after 3 days without NE, glands could be stimulated to produce melatonin when NE was added to the medium. When incubated with 10 μM NE for 6 hr in static culture, glands from 11‐ versus 4‐day‐old neonates produced 20 times more melatonin and had over three times higher NAT specific activity. After a 15 min incubation with 10 μM NE, cAMP content was three‐fold higher in 11‐compared to 4‐day‐old pineals. Our results demonstrate that although the pineal's response to NE increases with age, its response time is invariant throughout postnatal development.