Characterization of Human Melatonin Synthesis Using Autoptic Pineal Tissue

Mar 25, 2006Endocrinology

Understanding how melatonin is made in the human pineal gland after death

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Abstract

A significant correlation exists between time of death and both AA-NAT activity and melatonin content, with elevated values during dusk and night.

The mammalian pineal gland synthesizes melatonin, which signals the duration of nighttime.
In humans, the regulation of melatonin synthesis mechanisms remains unclear compared to rodents.
RNA degradation rates for genes of interest were consistent, allowing for reliable normalization of data regardless of postmortem delay.
No diurnal rhythm was observed for Aa-nat and Hiomt mRNA levels or HIOMT activity.
The findings suggest that transcriptional regulation may not be the primary mechanism for rhythmic melatonin synthesis in the human pineal gland.

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The mammalian pineal gland synthesizes rhythmically the hormone melatonin, which provides the body with a signal coding the duration of the night period. The ultimate enzymatic step in melatonin synthesis is achieved by the hydroxyindole O-methyltransferase (HIOMT); the rate-limiting enzyme is, however, the arylalkylamine N-acetyltransferase (AA-NAT). In contrast to the central importance of a transcriptional regulation of the Aa-nat gene for rodent melatonin synthesis, mechanisms in the human pineal gland are elusive. Therefore, pineal tissue, taken from regular autopsies (n = 69; postmortem intervals ranging from 9 to 147 h) was analyzed simultaneously for Aa-nat and Hiomt mRNA levels by PCR, AA-NAT activity using (14)C-acetyl-coenzyme A, HIOMT activity using S-adenosyl-l-[(14)C]-methionine, and melatonin content using an ELISA. Results were allocated to asserted time-of-death groups (day, 1,000 to 1,630 h; dusk, 1,630 to 2,200 h; night, 2,200 to 0730 h; dawn, 0730 to 1,000 h). RNA degradation rates of genes of interest ran in parallel, and, therefore, data normalization could be established, regardless of postmortem delay in tissue sampling. Aa-nat and Hiomt mRNA and HIOMT activity showed no diurnal rhythm. In contrast, a significant rhythm was found for the correlation between time of death and both AA-NAT activity and melatonin content, with elevated values during dusk and night. Presented data demonstrate that postmortem brain tissue can be used to detect the remnant of premortem adaptive changes in neuronal activity. In particular, our results give strong experimental support for the idea that transcriptional mechanisms are not dominant for the generation of rhythmic melatonin synthesis in the human pineal gland.

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Characterization of Human Melatonin Synthesis Using Autoptic Pineal Tissue

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