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Differential somatostatin receptor subtype expression in human normal pineal gland and pineal parenchymal tumors
1INSERM U433, Faculté de Médecine RTH Laennec, Lyon Cedex, France. champier@laennec.univ-lyon1.fr
Abstract:
Somatostatin is a potent antiproliferative signal in both tumoral and normal mammalian cells, and altered somatostatin receptor (sst) expression is associated with carcinogenesis in human tissues. In this study, two normal and three tumoral human pineal glands were analyzed using the reverse transcriptase-polymerase chain reaction (RT-PCR) for the presence of mRNA coding for the five different somatostatin receptors (sst1-sst5). Pineal parenchymal tumor (PPT) differentiation was confirmed by immunohistochemical detection of neuroendocrine markers (synaptophysin, neurofilaments, and chromogranin A). The presence of mRNA coding for c-myc, a proto-oncogene, and for tryptophan hydroxylase (TPOH), serotonin N-acetyltransferase (NAT), and hydroxyindole-O-methyltransferase (HIOMT), enzymes of the melatonin pathway, was also analyzed by RT-PCR. Only the tumoral tissues contained c-myc mRNA. All five tissues contained TPOH, NAT, and HIOMT mRNA, the levels of HIOMT mRNA being lower in PPT than in the normal pineal gland, suggesting that PPT retain the ability to synthesize melatonin. All tissues contained sst1, sst2, and sst3 transcripts, but not sst4, while small amounts of sst5 mRNA were only found in normal pineal glands. Real-time PCR, performed only with the most abundant subtpe sst2, evidenced an about sixfold higher level in in normal pineal glands. These results demonstrate the presence of somatostatin receptors in the human pineal gland, as described in other species, and point to a differential expression of the sst2 and sst5 subtypes associated with carcinogenesis.
Insights
Somatostatin receptors (sst) are present in the human pineal gland. Their expression differs between normal and tumoral tissues, with sst2 and sst5 subtypes showing altered levels in pineal parenchymal tumors, indicating a role in carcinogenesis.
Area of Science:
- Neuroendocrinology
- Oncology
- Molecular Biology
Background:
- Somatostatin acts as an antiproliferative signal in mammalian cells.
- Altered somatostatin receptor (sst) expression is linked to human carcinogenesis.
- The human pineal gland's somatostatin receptor expression in relation to tumors is not fully understood.
Purpose of the Study:
- To investigate the expression of five somatostatin receptor subtypes (sst1-sst5) in normal and tumoral human pineal glands.
- To analyze the expression of c-myc proto-oncogene and melatonin pathway enzymes (TPOH, NAT, HIOMT) in these tissues.
- To determine if differential somatostatin receptor expression is associated with pineal parenchymal tumor (PPT) development.
Main Methods:
- Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect mRNA for somatostatin receptors (sst1-sst5), c-myc, and melatonin pathway enzymes.
- Immunohistochemistry confirmed PPT differentiation using neuroendocrine markers (synaptophysin, neurofilaments, chromogranin A).
- Real-time PCR quantified the expression of the most abundant subtype, sst2.
Main Results:
- All analyzed tissues expressed sst1, sst2, and sst3 mRNA; sst5 mRNA was found only in normal glands.
- Tumoral tissues uniquely contained c-myc mRNA.
- Pineal parenchymal tumors showed lower HIOMT mRNA levels but retained TPOH and NAT mRNA, suggesting some melatonin synthesis capability.
- Real-time PCR revealed approximately sixfold higher sst2 mRNA levels in normal pineal glands compared to tumoral tissues.
- sst2 and sst5 expression levels were significantly different between normal and tumoral pineal glands.
Conclusions:
- The human pineal gland expresses somatostatin receptors, consistent with findings in other species.
- Differential expression of sst2 and sst5 somatostatin receptor subtypes is associated with human pineal parenchymal tumors.
- These findings suggest a potential role for somatostatin receptor modulation in the context of pineal gland carcinogenesis.
