Cells expressing preproenkephalin mRNA in the rat pineal gland are not serotonin-producing pinealocytes: evidence using in situ hybridization combined with immunocytochemistry for serotonin.

1. Preproenkephalin (PPEnk) mRNA expressing cells have been identified in rat pineal gland using radioactive in situ hybridization histochemistry. 2. Approximately 7% of the cells in the pineal gland (7.5 +/- 0.86, mean +/- 95% CI) express PPEnk mRNA. These cells are distributed throughout the pineal as either scattered single cells or small groups of cells with large round or oval nuclei. 3. Using in situ hybridization combined with ABC immunocytochemistry for serotonin (5-HT) in the same pineal sections, the PPEnk mRNA labeling cells are found not to be serotonin-immunoreactive cells. These data indicate that the PPEnk mRNA is expressed in a certain discrete subpopulation of cells in the rat pineal gland and these cells are not serotonin-producing pinealocytes. 4. The physiologic role of PPEnk-derived peptides in the pineal remains unknown. It is possible that these peptides either are synthesized and secreted as hormones or act as pineal paracrine signals.