The content of C-Fos protein was tested in rat pinealocytes
in the norm and stress and in case of intranasal administration
of Epitalon (Ala-Glu-Asp-Gly), which regulated pineal secretion
processes, presumably, via protooncogenes.
Intact and osmotic-stress-exposed rats were used for the immunohistochemical
detection of C-Fos protein. All animals were intranasally
administered with Epitalon, the last infusion made in two
hours before the biopsy. Simultaneously, light microscopy
of the pineal parenchyma was performed in all groups of animals.
A slight but significant C-Fos increase was observed only
in stress-exposed pinealocytes of rats after intranasal Epitalon
infusions. C-Fos was irregularly distributed throughout pineal
cells. In stress, the clusters of 510 cells containing
C-Fos in their cytoplasm were detected. The dilation of capillaries
and pericapillary space induced by an osmotic stress was partially
reduced by the intranasal infusions of Epitalon.
Tetrapeptide Epitalon is synthesised on the basis of the amino
acid composition of pineal peptide extract Epithalamin. Epitalon
modulates pineal secretion only under a stress impact but
never in the norm. It prevents osmotic-stress-induced pathologic
changes in the pineal parenchyma structure. Besides, the physiological
activity of Epitalon seems to be mediated by the activation
of protooncogenes in pinealocytes.
the pineal gland and the hypothalamus-hypophysis complex take
part in the formation of general adaptation syndrome [1, 2].
Stress causes the pineal gland to increase the secretion of
melatonin and peptide substances [2, 11], which are known to
reduce the damaging effect of oxygenic, osmotic, psychic and
other stresses. The peak of pineal melatonin secretion occurs
only at night, while in the daytime pinealocytes secrete other
substances, peptides in particular. Yet, the works dedicated
to pineal peptides are disproportionally few as compared to
available publications on melatonin.
The pineal gland belongs to circumventricular organs having
no blood-brain barrier. Consequently, this organ is highly sensitive
to macromolecular biologically active substances circulating
with the cerebral blood flow and, especially, to peptides. The
unique location of the olfactory system, its chemical links
both to the environment and the central nervous system turn
it to a convenient pathway for the non-invasive delivery of
substances to the cerebral blood flow and circumventricular
organs. This pathway bases on the anatomic connection of the
nasal submucosa to the subarachnoid space surrounding olfactory
nerves as they penetrate the cribriform plate of the skull and
enter the brain . The cribriform region has no significant
barrier to cerebrospinal fluid drainage [3, 8]. This is the
possible way for metals, dyes, viruses, peptides [14, 15], proteins
and narcotics to enter the brain via nasal cavity avoiding the
blood-brain barrier . Previously we have shown that intranasally
infused epiphyseal peptides reach the pineal gland and specifically
regulate its electric activity and pinealocytic ultrastructure.
Furthermore, these effects have been observed only in stress,
but not in the norm . An important role in intracellular
pineal synthesis activation, for example, in stress, belongs
to heterodimer AP-1 formed of C-Fos and C-Jun transcription
factors [10, 13]. C-Fos protein exists longer than its mRNA.
The peak of its content in the cytoplasm is usually observed
in two hours after, for instance, a stress impact. Some authors
 have suggested cytomedins to influence the cells through
C-Fos synthesis activation. To prove the hypothesis on the participation
of oncogenes in the pineal humoral self-regulation, we have
performed an immunohistochemical detection of C-Fos protein
in the pinealocytes of stress-exposed rats subjected to the
intranasal infusions of Epitalon.