Circadian
rhythm of melatonin in postmenopausal asthmatic women with
hormone replacement therapy
Beata
Kos-Kudla 1, Zofia Ostrowska 2, Bogdan Marek 1, Dariusz Kajdaniuk
1, Nelly Ciesielska-Kopacz 3, Marek Kudla4 Bogdan Mazur 1,
Joanna Glogowska-Szelag 1 & Maja Nasiek 1
1.
Department of Pathophysiology and Endocrinology,
2. Department of Clinical Biochemistry,
3. Department and Clinic of Internal and Allergic Diseases,
Silesian Medical University, Zabrze, Poland.
4. III Dept.& Clinic of Obstetrics and Gynaecology, Silesian
Medical University, Katowice, POLAND.
Submitted:
September 30, 2001
Accepted: February 28, 2002
Keywords:
melatonin; circadian rhythm; hormone replacement therapy;
asthma bronchiale
Abstract
OBJECTIVE:
The aim of the study was to check if in postmenopausal women
such a disease as asthma and use of hormone replacement therapy
(HRT) influence daily melatonin (MEL) secretion.
MATERIAL
AND METHODS:
Studies were performed in 55 asthmatics (treated and not treated
with glucocorticosteroids) and 20 healthy postmenopausal women
(aged 48–60) before HRT and after 6 months of transdermal
17b-estradiol and medroxyprogesterone acetate treatment (cyclical
method). During the circadian study blood samples for the
measurement of MEL were collected every 3 hours during the
day. MEL concentrations were assessed with the use of RIA
methods. Statistical analysis of the circadian rhythm was
performed with the use of cosinor test according to Halberg
et al.
RESULTS:
Existence of daily rhythm of MEL secretion was shown in all
studied groups, before as well as after HRT. A significant
decrease of mesor and amplitude's rhythm was observed in the
group of women with asthma treated with glucocorticosteroids
(GC) before and after HRT use in relation to women not treated
with GC and the control group. Secretion of MEL in these patients
was lower at nocturnal hours. A significant decrease of mean
daily MEL secretion in relation to values before HRT use was
shown in all groups.
CONCLUSIONS:
Asthmatic postmenopausal women treated with GC show lowered
circadian secretion of melatonin as a consequence of lowering
its secretion at nocturnal hours. Hormonal replacement therapy
causes a decrease of daily melatonin secretion in healthy
as well as asthmatic women, not disturbing circadian rhythm
of this hormone's secretion.
Introduction
ABBREVIATIONS
A - amplitude
E2- estradiol
GC - glucocorticosteroids
GnRH - gonadotropin-releasing hormone
HPA - hypothalamo-pituitary-adrenal
HRT - hormone replacement therapy
M - mesor
MEL - melatonin
LH - luteinizing hormone
p - probability
RIA - radioimmunological methods
j - acrophase
w - angular frequency
Introduction
The role of melatonin (MEL) in both physiological and pathological
states in humans remains unclear.
The best-documented role of MEL is regulation of the circadian
rhythm of biological processes. It may have a variety of other
functions: free radical scavenger, transitional metal chelation,
immuno-stimulation, neuroprotection, antitumor and osteoblast
promotion [1]. MEL levels fall markedly with ageing, and may
contribute to the incidence or severity of some age-associated
neurodegenerative diseases [2].
Several
lines of evidence indicate that ageing and gonadal steroids
influence biological responses to MEL. Gonadal steroids modulate
the number of MEL receptors in animals and influence LH, cortisol
and body temperature responses to exogenous MEL in humans [3].
A
direct modulatory effect of the gonadal hormones on pineal MEL
synthesis is well established in animal studies. In the case
of humans abnormal MEL release associated with disorders of
the reproductive system can only be argued in the presence of
compelling evidence suggesting a relationship between MEL and
hypothalamo-pituitary-gonadal axis. The demonstration of MEL
receptors on different gonadal cells from various species as
well as seasonal variation in gonadotropins and gonadal steroids
receptors in the human pineal gland and negative significant
correlation between the peak serum MEL and serum 17b-estradiol
in perimenopausal women further strengthen the relationship
between MEL and reproductive hormones, although it is not known
whether these receptors and their ligands are crucial to pineal
MEL secretion [4]. Recent studies indicate also other connections
between MEL and estrogens significant for organism. Estrogens
exert pro-oxidative effects and have been shown to damage DNA,
potentially leading to cancer. MEL is a well-known antioxidant
and oncostatic agent. Studies on animals confirmed the dual
actions of estrogens relative to oxidative damage, i.e., estrogen
increases oxidative destruction of DNA while reducing lipid
peroxidation. MEL had antioxidative actions in reducing oxidative
damage to both DNA and to membrane lipids. MEL completely prevented
the damaging action of E2 on DNA and synergized with the steroid
to reduce lipid peroxidation [5].
It
has been reported that several biological responses to MEL can
be influenced by the estrogenic and possibly progestogenic environment,
and are sometimes inconsistent in elderly postmenopausal women
[6].
There is still a considerable amount of uncertainly related
to the application of hormone replacement therapy (HRT) regarding
its influence on hormonal changes occurring in the organism
of healthy women as well as in the course of many diseases in
the postmenopausal period. There are also few reports concerning
the influence of HRT on MEL secretion in this period.
Cagnacci
et al. [3] indicated the circulatory response to MEL is conserved
in postmenopausal women with, but not without, HRT. Maintenance
of the cardiovascular response to MEL may be implicated in the
reduced cardiovascular risk of postmenopausal women with HRT.
MEL influences vascular reactivity and reduces blood pressure
and norepinephrine levels [7]. The same authors [3] also observed
that MEL does not modulate adrenergic activity in postmenopausal
women without HRT. Estradiol replacement restores the capability
of MEL to modulate adrenergic activity, particularly the norepinephrine
response to stimuli.
Because
the postmenopausal period condenses age- and hypoestrogenism-related
biological modifications, we investigated whether in postmenopausal
women disease such as asthma and use of HRT influence daily
MEL secretion
Material and methods
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