The primary source of circulating melatonin in adult mammals is the pineal gland (38). Melatonin levels are elevated at night. As reviewed in detail elsewhere in this volume, melatonin production from the pineal is regulated by the circadian clock in the suprachiasmatic nuclei. Other tissues appear capable of producing melatonin. Melatonin is produced rhythmically in the retina, but the retina does not appear to contribute significantly to circulating melatonin levels in rodents. N-acetyltransferase activity and NAT gene expression occur in other tissues, including brainstem and pituitary (12). With precursor loading it is possible to detect significant production of melatonin in the gastrointestinal tract, although melatonin synthesized in the gastrointestinal tract does not appear to contribute to circulating levels of the hormone (24). It is nevertheless possible the local production of melatonin within the abdomen may provide a pool capable of reaching the fetus.
The primary source of melatonin for the developing mammal is the maternal pineal gland. The melatonin rhythm in maternal circulation is accurately reflected in the fetus, allowing melatonin to serve as a "chrono-pheromone." Melatonin levels in fetal plasma closely parallel those in maternal plasma, and rapid transfer of melatonin across the placenta has been demonstrated in several species including rodents, sheep, and non-human primates (34,59,69,86,87,89). Furthermore, maternal pinealectomy abolishes the rhythm of melatonin in fetal circulation (46,87; see Figure 2).
Maternal melatonin also reaches the developing animal after birth. Transfer of melatonin from mother to offspring in milk has been demonstrated (50), and rhyth-micity of serum melatonin levels in suckling rats appears due to transfer of maternal melatonin via the milk (69).
Rhythmic melatonin production from the developing pineal is first significant during the second to third week of postnatal life in rodents (67). In sheep and humans, rhythmicity of melatonin levels in serum, originating in the developing pineal gland, also begins during the postnatal period (2,11,46).
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