Regulation of melatonin synthesis in the ovine pineal gland

The results presented here show clearly that the rapid nocturnal increase in circulating melatonin in sheep is associated with an equally rapid increase in melatonin production in the pineal gland. Pineal NAT activity and NAS concentration also increased under this condition, indicating that NAT activity is an important factor in this process. According to the current model for the regulation of pineal melatonin production in the rat, the large nocturnal increase in NAT activity is the major factor responsible for the daily rhythm in melatonin, as well as for the opposite rhythm in serotonin and its oxidation products in the pineal gland. Increased NAT activity in the pineal gland at night channels serotonin toward melatonin production at an enhanced rate, thereby causing pineal serotonin levels to drop. This, in turn, leads to decreased production of oxidative metabolites due to reduced substrate availability for MAO. Thus, the large increase in NAT activity acts as the key factor, directly or indirectly, for the generation of all rhythms in serotonin metabolites in the pineal gland, and possibly in the circulation. Such an exclusive role for NAT is doubtful in the sheep pineal gland for the following reasons: First, the nocturnal increase in NAT activity is relatively small (3-5-fold) compared to the rat (50-100-fold). Second, in at least two instances--a 30 min light pulse and prazosin treatment--there was a clear dissociation between melatonin production and NAT activity. This lack of correlation between NAT activity and melatonin production does not seem to be due to serotonin availability since serotonin levels did not change under the above conditions. Further, serotonin levels were found to decrease rather than increase when melatonin levels increased at night. Finally, our observation that melatonin production can be increased during the day by increasing serotonin levels in the pineal gland may reflect only the incompletely saturated nature of pineal NAT and may have little relevance for the physiological regulation of pineal melatonin production. Even though NAT activity may not be the only factor responsible for the rhythmic production of serotonin metabolites in sheep pineal gland, activation of the serotonin----melatonin pathway seems to be the primary metabolic response involved in this regulation, since the rhythms in the serotonin metabolites are similar in both rat and sheep. In the rat, the activation of the serotonin----melatonin pathway is brought about exclusively by the increase in NAT activity.(ABSTRACT TRUNCATED AT 400 WORDS)