NEUROENDOCRINOLOGY
LETTERS including Psychoneuroimmunology, Neuropsychopharmacology,
Reproductive Medicine, Chronobiology
and
Human Ethology
ISSN 0172–780X
Saint-Petersburg Institute of Bioregulation and Gerontology
of the North-West Branch of the Russian Academy of Medical
Sciences, St.Petersburg, RUSSIA.
In last two decades there are more and more evidences that identical
peptide hormones and biogenic amines are synthesized by different
cells having neuronal, immune or endocrine assignment. Historically,
Pearse was the first who in the late 1960’s suggested that
a specialized, highly organized cell system should exist in
organisms, whose main feature was the ability of component cells
to produce peptide hormones and biogenic amines. His concept
was based on an extensive series of experiments for distinguishing
endocrine cells in different organs, identifying endocrine cell-generated
products and performing a thorough cytochemical and ultrastructural
analysis of these cells. Pearse has shown that a variety of
cell types, widely dispersed throughout the organism, have a
common ability of absorbing monoamine precursors (5-hydroxytryptophan
and L-dihydroxyphenylalanine) and decarboxylating them, thus
producing biogenic amines. This ability accounts for the term
APUD, an abbreviation of “Amine Precursor Uptake and Decarboxylation”
used by Pearse to designate this cell series [1,2].
To
date, the APUD series includes over 60 types of endocrine cells
located in gut, pancreas, urogenital tract, airway epithelium,
pineal gland, thyroid gland, adrenals, adenohypophysis and hypothalamus,
carotid body, skin, sympathetic ganglia, thymus, placenta and
other organs. Meanwhile the advent of radioimmunological methods
and the rapid development of immunohistochemistry resulted in
the establishment of a completely unexpected phenomenon, i.e.,
the same biogenic amines and peptide hormones were identified
in neurons and endocrine cells. This year, 2002 marks the 25th
Anniversary since Roger Guillemin had been awarded a Nobel Prize
and presented his Nobel Prize Lecture entitled “Peptides
in the brain. New endocrinology of the neuron” [3].
The
accumulated data did not fit the traditional concepts of hierarchical
dependence within two main regulatory systems, viz., the nervous
and endocrine systems. It became more and more evident that
the mechanism of biological regulation should be based on the
coordinated functional interaction between the endocrine system
and the central and peripheral nervous systems considering the
common type of information perception and transmission at subcellular,
cellular and tissue levels. Many studies on identification of
the same and similar physiologically active substances, acting
within the nervous system as neurotransmitters and neurohormones,
and locally or remotely as hormones within the endocrine system,
enables both systems to be incorporated into the universal diffuse
neuroendocrine system (DNES) [4]. Actually,
it should be possible to unite in the organisms the structurally
isolated nervous and endocrine systems by means of the functional
relationships between biogenic amines and regulatory peptides
and, to a certain extent, to provide a basis for the concept
of integrated functions. Located in practically all organs and
producing biologically active substances, the DNES cells play
role of regulators of homeostasis acting via neurocrine, endocrine
and paracrine mechanisms [5].
Later it was shown that the nervous and immune systems have
well-established and very closely related interactions which
regulate systemic homeostasis involving the production and secretion
of a variety of cellular mediators known as regulatory peptides
(peptide hormones, cytokines, chemokines, integrins and others)
[6]. Peptide hormones, cytokines and other
related molecules regulate homeostasis in the tissue of origin,
either via local actions or by recruitment of external systems
that facilitate restoration of local homeostasis. Studies on
isolated-cell systems have confirmed that many regulatory peptides
and biogenic amines are expressed within the brain. There are
many peptidergic neurons and glial cells in the brain which
can produce peptide hormones and biogenic amines; also besides
neurons, immune cells, such as macrophages, T-lymphocytes, eosinophilic
leukocytes and mast cells, which invade the brain after injury
or inflammation, are a rich source of cytokines and other active
molecules [7-9].
Such common chemical characteristics of three regulatory systems,
namely: nervous, endocrine and immune systems stimulated the
development of a new research field called neuroimmunoendocrinology
which mainly studied the mutual interrelationships between these
regulatory systems [10]. It seems necessary
to underline that numerous investigations in this field of study
fail to take one phenomenon into account which we consider as
a very important fact: the nervous and immune cells together
with APUD cells are present in most visceral organs, where they
are available to produce many peptides and biogenic amines which
are identical to the same in the brain and central organs of
the immune and endocrine systems (Figure).
Therefore,
the close interrelationships between the three regulatory systems
provide with anatomical/functional property - immune and nervous
system have their representation in visceral organs through
the peptidergic/aminergic neurons (and/or nerve fibers) as well
as through the immunocompetent cells producing different peptide
molecules; in its turn, the endocrine system represents in the
central nervous system and immune organs through APUD cells
(e.g. hypothalamic neurosecretory cells and others).
Thus,
it is obvious that cell types of all three classical regulatory
systems (nervous, endocrine and immune) are represented in each
visceral organ, including the central organs of homeostatic
regulation (e.g. brain, thymus, thyroid, etc).
Hence
it follows to be possible to unite peptidergic/aminergic neurons,
APUD cells and peptide-producing immunocompetent cells into
a single common functional system and to extend the term diffuse
neuroendocrine system (DNES) to a new term DIFFUSE
NEUROIMMUNOENDOCRINE SYSTEM (DNIES).
Exactly the DNIES is a field of the study for neuroimmunoendocrinology
(Figure) as a new scientific biomedical discipline which integrates
our knowledge about the signaling mechanisms of homeostatic
regulation.
Acknowledgements
This point of view is partly based on the results of our investigation
in the framework of the project supported by the Russian Foundation
of Basic Research (01-04-48238).
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