Histological features and expression of enzymes implicated in melatonin synthesis in pineal parenchymal tumours and in cultured tumoural pineal cells

Nov 1, 2007Neuropathology and applied neurobiology

Tissue features and melatonin-making enzymes in pineal gland tumors and tumor cells grown in the lab

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Abstract

All 10 pineal parenchymal tumours (PPT) contained messenger RNA (mRNA) for c-myc.

mRNAs for the enzymes involved in melatonin synthesis—tryptophan hydroxylase (TPH), arylalkylamine N-acetyltransferase (AANAT), and hydroxyindol-O-methyltransferase (HIOMT)—were detected in all PPT samples.
Only PPT expressed TPH protein, indicating a potential for these tumours to synthesize melatonin.
Cultured tumour cells exhibited a loss of transcript expression over passages, despite maintaining characteristic organelles.
A basal secretion of melatonin was observed in one culture of PPT cells, suggesting continued melatonin production, although stimulation with a beta noradrenergic agonist did not enhance production.
The papillary tumour of the pineal region (PTPR) did not express mRNA for TPH, AANAT, or HIOMT.

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Pineal parenchymal tumours (PPT) are rare neoplasms and there have been few in vitro studies. Their capacity for synthesizing and secreting melatonin has been only partially examined. We investigated the presence of messenger RNA (mRNA) encoding tryptophan hydroxylase (TPH), arylalkylamine N-acetyltransferase (AANAT), hydroxyindol-O-methyltransferase (HIOMT), three enzymes involved in melatonin synthesis, and c-myc, a tumoural marker, in 10 PPT, one papillary tumour of the pineal region (PTPR), cell cultures derived from four PPTs and from three other tumours of the pineal region, and in normal pineal gland. Moreover, protein expression of TPH was investigated in three PPT and PTPR. Quantitative real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry were used and the melatonin production by tumoural cells in vitro was analysed by radioimmunoassay. We showed that all the tumoural tissues and cells contained c-myc mRNA. mRNAs encoding TPH, AANAT and HIOMT were detected in all PPT, suggesting that tumour cells can synthesize melatonin. Only PPT expressed TPH protein. Cultured cells lost expression of transcripts throughout passages even if ultrastructural study revealed the presence of characteristic organelles in these tumoural cells. Nevertheless, the basal secretion of melatonin observed in one PPT culture is in favour of a maintained melatonin production and secretion by tumoural pinealocytes, but melatonin production was not stimulated by a beta noradrenergic agonist. Moreover, PTPR never expressed mRNA encoding TPH, AANAT and HIOMT. Our results may contribute to a better understanding of the biology of PTT and PTPR and may help to the diagnosis of these rare tumours.

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Histological features and expression of enzymes implicated in melatonin synthesis in pineal parenchymal tumours and in cultured tumoural pineal cells

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