Biomedical Engineering Reference
In-Depth Information
synthesis does not require the acetylation of
serotonin, the nocturnal increase in pineal SNAT
activity may not be related to the rise in pineal
methoxyindole levels. The intraparenchymal
release of stored pineal serotonin which then
becomes accessible to both SNAT and MAO ulti-
mately controls the rates at which these three
major pineal methoxyindoles are synthesised and
generates the nocturnal increases in pineal mela-
tonin and 5-methoxytryptophol. The rates of
methylation of all three 5-hydroxyindoles formed
from pineal serotonin depend on HIOMT activity
in pineal gland. The proportion of available sero-
tonin acetylated at any particular time of day or
night depends on the relative activities of pineal
SNAT and MAO at that specific time.
Melatonin has been found in blood, urine and
saliva, also in the cerebrospinal fluid (CSF), at a
concentration much higher than in blood, and in
the anterior chamber of the eye (Martin et al.
1992
) .
Melatonin is also found in semen, amniotic fluid,
urine and breast milk (Cagnacci
1996
) . Melatonin
in plasma, CSF, saliva and urine is eliminated by
pinealectomy, indicating that it is mainly synthe-
sised in the pineal gland (Nelson and Drazen
1999
) . There is, however, evidence that melatonin
is also synthesised at other sites which include,
in humans, the retina, gut and bone marrow
(Cagnacci
1996
; Conti et al.
2000
) , indicating a
localised action of melatonin besides a central
regulatory function (Fjaerli et al.
1999
) .
et al.
1992
), prostate epithelial cells (Zisapel et al.
1998
) , granulose cells of preovulatory follicles
(Yie et al.
1995
), spermatozoa (van Vuuren et al.
1992
), the mucosa layer of the colon (Poon et al.
1996
) and blood platelets (Vacas et al.
1992
) . In
the absence of receptors, melatonin molecules
exert systemic effects also at the basic cellular
levels (Benitez- King
1993
; Fjaerli et al.
1999
) .
6.3
Daily Rhythm of Melatonin
The daily alternation of light and dark is the most
important regulatory element in the synthesis of
pineal hormone melatonin. In all mammals
studied, whether they exhibit nocturnal or diurnal
activity, melatonin levels are higher at night than
during the day. The melatonin level starts to rise
during the evening and is at its highest in the mid-
dle of the night and starts to decrease reaching
low levels in the morning. The daily rhythm of
melatonin is considered to be a very reliable
phase marker used by the endogenous timing
system. The study on zebu-cross heifers reported
that plasma melatonin level was observed to be
the lowest at 12.30 h (23.33 ± 5.78 pg/ml) during
day, and thereafter, an increase in plasma mela-
tonin level was observed (after 20.30 h) with
increase in darkness and the mean peak level
(124.33 ± 16.16 pg/ml) occurred at 00.30 h dur-
ing night (Aggarwal et al.
2005
; Fig.
2
). The level
declined and was low during daytime. There was
a signi fi cant (
P
< 0.05) variation in plasma mela-
tonin levels during different times of the day.
In the absence of the light-dark cycle, mela-
tonin rhythms do not exhibit characteristic pat-
tern and observed to free run with a period slightly
different from 24 h (Aschoff
1965
) . In rats, Syrian
hamster and Siberian hamster (
P. sungorus
),
pharmacological doses of exogenous melatonin
are capable of synchronising the circadian
rhythms of locomotor activity and melatonin syn-
thesis in free-running circadian rhythms (Redman
et al.
1983
; Schuhler et al.
2002
) . Lesioning of the
SCN abolishes pineal melatonin rhythm (Klein
and Moore
1979
). Therefore, input from the main
endogenous circadian pacemaker, located in
the SCN, is essential for the circadian rhythm of
6.2
Melatonin Receptors
In humans, there are two types of melatonin
receptors (Mel1a and Mel1b) with different
binding affinity and chromosomal localisation
(Reppert et al.
1995
) . Melatonin receptors have
been found in the SCN of the hypothalamus,
which controls the rhythmic production of mela-
tonin by the pineal gland (Reppert et al.
1988
;
Weaver and Reppert
1996
). In addition, it is also
located in the cerebellum (Al-Ghoul et al.
1998
) ,
retinal rods, horizontal amacrine and ganglion
cells (Reppert et al.
1995
; Scher et al.
2002
) .
Besides the CNS, human melatonin receptors
have been found in lymphocytes (Lopez-Gonzalez
