Melatonin synthesis and melatonin‐membrane receptor (MT1) expression during rat thymus development: role of the pineal gland

Abstract

To gain insight into the relationship between thymus and pineal gland during rat development, the melatonin content as well as the activity and expression of the two key enzymes for melatonin biosynthesis, i.e. N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT), were studied in the thymus at fetal and postnatal stages. Moreover, melatonin-membrane receptor (MT1) expression was also analyzed. We found both the expression and activity of thymic NAT and HIOMT at 18 days of fetal life. Additionally, there is production of melatonin in the thymus as well as MT1 expression at this fetal age. These results show values higher in day-time than at night-time. The pineal gland begins to produce significant levels of melatonin around postnatal day 16, and this synthesis shows a circadian rhythm with high values during the dark period; therefore the nocturnal serum melatonin may inhibit thymic melatonin production. To document this, we report an increased melatonin content of the thymus in pinealectomized rats compared with sham-pinealectomized. In conclusion, these results show, for the first time, the presence of the biosynthetic machinery of melatonin and melatonin production in developing rat thymus and that the pineal gland may regulate this process.

Melatonin biosynthesis in the thymus of humans and rats

“…Presence of melatonin receptors in thymus completes the evidence of this relationship [44 -46]. Recently, our group has described an endogenous melatonin biosynthesis in rat thymus during development [47]. In the present work, we probe deeper into melatonin production in thymus of adult rats, carrying out additional studies, as well as demonstrating, for the first time, a melatonin synthesis in thymus of humans.…”

“…Our findings, although a bloodstream melatonin retention cannot completely be ruled out, demonstrate an endogenous biosynthesis in rat thymus, as the AA-NAT and HIOMT mRNAs are expressed and give rise to active enzymes, and thymocytes in culture exhibit high levels of melatonin. Moreover, a recent study of our group showed that pinealectomized rats have a clearly increased thymic melatonin content [47], evidencing an endogenous synthesis, and suggesting that either pineal melatonin could be inhibiting thymic synthesis of melatonin and/or, when pinealsynthesized melatonin is absent, the thymus could show a compensatory rise in melatonin production. Experiments in humans showed a high level of melatonin in thymus homogenate (Fig.…”

The Immunoendocrine Thymus as a Pacemaker of Lifespan

“…The effect of pineal to thymus could be done by pineal peptides [127] or melatonin. It seems likely a functional unity of pineal and thymus involution [79,124,128]. The functional unity is also supported by human experiments, when durable combined treatment with pineal and thymus peptides prolonged the lifespan [129].…”

Expression of tranferrin receptors in the pineal gland of postnatal and adult rats and its alteration in hypoxia and melatonin treatment

“…The mRNA levels are significantly (* P < 0.05) decreased after melatonin treatment. (Jimenez et al, 2005) and the circadian variation of melatonin content in the pineal gland appears during the 3rd week of extrauterine life (Velazquez et al, 1992). Ultrastuctural observations in the rat pineal gland showed that the pinealocytes adopted an adult morphological appearance around 20 days of age when the circadian melatonin rhythm appeared (Blazquez et al, 1989).…”