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 microM 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 microM 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 microM 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 microM 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 microM 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.