NEUROENDOCRINOLOGY
LETTERS including Psychoneuroimmunology, Neuropsychopharmacology,
Reproductive Medicine, Chronobiology
and
Human Ethology
ISSN 0172–780X
Circadian
rhythm of melatonin in patients with colorectal carcinoma
Beata
Kos-Kudla1, Zofia Ostrowska2, Andrzej Kozlowski3, Bogdan Marek1,
Nelly Ciesielska-Kopacz4, Marek Kudla5, Dariusz Kajdaniuk1,
Janusz Strzelczyk1 & Pawel Staszewicz1
1. Department of Pathophysiology and Endocrinology,
2. Department of Clinical Biochemistry,
3. 2nd Department of General and Vascular Surgery,
4. Department and Clinic of Internal and Allergic Diseases,
Silesian Medical University, Zabrze, Poland
5. III Dept.& Clinic of Obstetrics and Gynaecology, Silesian
Medical University, Katowice, POLAND
Submitted:
January 4, 2002
Accepted: March 6, 2002
OBJECTIVE:
The aim of the study was pineal gland function assessment
on the base of daily rhythm study and mean daily melatonin
(MEL) concentrations in serum in patients with colorectal
carcinoma.
MATERIAL
AND METHODS: Studies were performed in 12 women
at the age of 63.17±5.90 years and 21 men aged 58.95±11.32
years with large intestine adenocarcinoma. The control group
consisted of 28 healthy volunteers at comparable age. During
the circadian study blood samples for the measurement of melatonin
(MEL) were collected every 4 hours during 12 h. MEL concentrations
were assessed with the use of RIA methods. Statistical analysis
of circadian rhythms of MEL was carried out with the use of
cosinor method according to Halberg.
RESULTS:
Existence of daily rhythm of MEL secretion was shown in all
studied groups. A significant decrease of amplitude of rhythm
and secretion of MEL at nocturnal hours in comparison with
the control group was shown in the group of women with large
intestine carcinoma. A significant decrease of mesor value
and amplitude of MEL rhythm as a consequence of decrease of
MEL secretion at nocturnal and morning hours was observed
in the group of ill men.
CONCLUSIONS:
Decrease in melatonin circadian rhythm amplitude as a consequence
of its lowered nocturnal secretion occurred in all patients
with colorectal carcinoma. Abnormalities in daily rhythm of
melatonin secretion were more intensified in men with large
intestine carcinoma, which leads to suppression of mean daily
hormone concentration.
Introduction
Recent
studies, both experimental and clinical indicate connections
between the pineal gland and neoplastic growth. The pineal gland
is called an oncostatic organ. The presence of melatonin (MEL)
receptors in different types of malignant tumors has been shown,
among others in patients with large intestine carcinoma [1,2,3].
It was suggested that melatonin may influence the human colonic
functions through interaction with its receptors in the mucosa
[3].
The mechanism of oncostatic action of MEL is still not precisely
explained. MEL may act through the endocrine system, immune
system, regulating interaction of the pineal gland and opioid
system, and exerting direct antiproliferative action [5]. Cos
and Blask [4] hypothesized that melatonin can inhibit action
and/or release of growth factors stimulating development and/or
growth of tumor cells. It was shown in vitro that MEL inhibits
tumor growth stimulated by epidermal growth factors (EGF) and
insulin-like growth factor (IGF-I). IGF-I takes part in the
promotion of normal and neoplastic cells growth. Most probably
it also plays a role in processes of neoplastic transformation,
angiogenesis, and progression of neoplasm, in this in metastases
forming [4]. The mechanism of oncostatic action of MEL can also
be connected with antioxidant and scavenging free radicals properties
of MEL. Free radicals are considered an essential factor in
pathogenesis of neoplastic disease. It was shown that MEL is
a scavenger of hydroxyl and peroxyl radicals [6–7].
The mechanism of oncostatic action of MEL may also be connected
with immunopotentiating action of the hormone [8]. MEL stimulates
activated lymphocytes T to synthesis and release of endogenic
opioids, interleukin –2 and g- interferone [9]. Lissoni
et al. [10] have observed that MEL administration causes inhibition
of tumor development in patients with neoplasm of large intestine,
liver, stomach, pancreas and lungs with simultaneous increase
of the relation of lymphocytes T4 to T8.
MEL exerts an inhibiting influence on development and/or growth
of many types of tumors induced experimentally or transplanted
in animals [5,11]. There are only a few studies concerning the
assessment of MEL concentrations in different types of malignant
tumors in humans [12–17].
Trials to use therapy with MEL in advanced neoplastic disease
were also undertaken, obtaining encouraging effects. There is
a suggestion that MEL, except oncostatic action, can be useful
in the improvement of the quality of life in patients with incurable,
advanced malignant tumors [10,18–20].
The aim of the study was estimation of circadian rhythm and
mean daily serum MEL concentrations in patients with colorectal
carcinoma.
