Calretinin (CR) is a calcium-binding protein, found in a variety of or
gans and systems such as the central nervous system and the pineal gla
nd. It was first thought to be a specific neuronal marker but this sel
ectivity is now in question since CR has been demonstrated in avian th
ymus, rat ovary, rat and guinea pig inner ear, rat testis, and chicken
and rat pineal gland. To contribute to the knowledge of the presence
of CR-positive cells in the pineal parenchyma of rat and other mammali
an including man, we performed immunocytochemistry on pineal glands of
gerbils, rats, goats, cows, and humans, using a CR anti-serum. To con
firm it was actually CR that was demonstrated, we performed Western Bl
ot analyses. Finally, to precisely identify the nature of CR-positive
cells we accomplished double-labelling immunofluorescence, using antis
era against some nerve cell specific cytosquelettal proteins such as M
AP-5, MAP-2, NF-L, NF-M, and NF-H. CR-positive cells were found in all
pineal glands studied. These cells all possess a round, oval, or poly
gonal-shaped perikaryon sending one or more processes of different len
gths into the glandular parenchyma. There is a lack of CR immunoreacti
vity in the nucleus and cell organelles while the cytosol contains a h
igh concentration of this protein. Nevertheless, there are some slight
differences between species, especially concerning the number of reac
tive cells and their relationships with different parenchymal structur
es such as blood vessels or acervuli. Among the CR-positive cells, onl
y a few were actually nerve cells, contributing probably to an intrins
ic innervation of the gland. The remaining CR-reactive cells seem to c
orrespond mostly to pinealocytes in a specific histophysiological stat
e and possibly to neuron-like cells. The significance of the CR-positi
ve cells in the pineal glands remains to be elucidated.