J. Biomedical Science and Engineering, 2011, 4, 462-471 JBiSE
doi:10.4236/jbise.2011.46058 Published Online June 2011 (http://www.SciRP.org/journal/jbise/).
Published Online June 2011 in SciRes. http://www.scirp.org/journal/JBiSE
The annual cycle of the pituitary-thyroid axis activity in
healthy men under prolonged cold air exposure
Evgeny Bojko, Anastasiya Kaneva, Natalya Potolitsyna
Department of Environmental and Social Human Physiology, Institute of Physiology Ural Division of Russian Academy of Sciences,
Syktyvkar, Russia.
Email: erbojko@physiol.komisc.ru
Received 23 April 2011; revised 10 May 2011; accepted 21 May 2011.
ABSTRACT
The monthly investigations of military guards ((19.1
0.9) years, n = 20) in northern European region (62N
lat.) that daily spent outdoors from 6 to 10 h were car-
ried out during the year (from November to October).
In examined subjects, the serum FT4 levels were high
enough during all period of research especially from
April till October when the hormone levels exceeded
norm. The concentration of serum FT3 was rather sta-
ble during the year and corresponded to the normal
level. At the same time, the levels of total form of thy-
roid hormone s (TT4 and TT3) displaced to lower limit
of norm. Thus, staying outdoors of military guards in
the North for all the year round is accompanied by
activization of thyr oi d hormones use.
Keywords: Thyroid Hormones; Human; Adaptation;
North; Cold
1. INTRODUCTION
The role of hormones regulating human energy metabo-
lism in cold condition has not been finally clarified. The
study of seasonally-related changes of the pituitary-
thyroid system status in human is interesting so far a
long time it was established that hormones of the thyroid
gland (TG) play main role in resistance of animal organ-
ism to cold [1-3]. It has been shown that single cold-air
or crushed ice exposure did not change the levels of se-
rum thyroxin (Т4) and thyroid-stimulating hormone
(TSH) in adult men [4,5]. It has been revealed that the
pituitary- thyroid axis in adult human subjects is insensi-
tive to short-time cold exposure that decreased the body
core temperature by 0.4 - 0.9[6]. At the same time,
immersion of adult subjects into cold water that de-
creased tympanic membrane temperature by 1 re-
sulted in twofold increase in the plasma TSH level for 90
min [7]. Repeated 30-min cold-air exposures for 2
months did not lead to changes in the Т4 and ТSH con-
centrations but decreased the level of serum total triio-
dothyronine (TT3) [8]. In another report, the decrease of
the serum total T4 (TT4) level at repeated cold-water
immersion was revealed [9].
The problem of prolonged and seasonal effects of
cold is especially important in relation to humans
permanently living in the North. The concept proposed
in previous studies suggested that the pituitary-TG axis
(Pit-TG) is activated during the cold season, which is
accompanied by an increase in the levels of serum TT3
and TT4 [10]. Later the increased T3 production has
been shown in Antarctic winterers [11,12]. At the same
time, it was noted in a number of reports that the level
of T4 remained unchanged during the year, whereas
TSH concentration increased in winter [13]. In north-
ern Finland, the T3 concentration in urine was in-
creased in the residents working outdoors from 6 to 10
h daily but there were no significant changes in the
levels of serum TT3, TT4, free T4 (FT4) and the T4
concentration in urine [14]. In winter, the free T3 (FT3)
level decreased in these subjects, whereas TSH level
increased (December), which in authors’ opinion might
be related to changes in illumination. The authors
agree that the thyroid hormones (TH) utilization was
increased in cold seasons but recognize that the tem-
perature effect was insignificant (the levels of TT3 and
TT4 were unchanged) and the opposite changes of TSH
and FT3 were not simultaneous [6]. The decrease of
FT3 level during wintering in Antarctica was shown [9].
At the same time, the decrease of TT3 production and
the increase of tissue availability of T3 during long-
term cold exposures were noted [8,9,12,15].
Our research of subjects that worked on Svalbard (78º
N) has shown that the levels of TT3 and TT4 increased
twice in the year during sharp change of intensity of the
light factor and depended on effect of day duration
change rather than on the duration of stay in the North or
air temperature [16,17]. Testing with a thyrotropin-re-
leasing hormone (TRH) load in winter showed that rep-
E. Bojko et al. / J. Biomedical Science and Engineering 4 (2011) 462-471
Copyright © 2011 SciRes. JBiSE
463
resentatives of aboriginal Northern populations were
characterized by a more pronounced activity of the cen-
tral part of Pit-TG system as compared to poorly adapted
subjects that were also born in the North [18].
Thus, there are still divergences in opinions of the
long-term cold-induced changes in the state of the Pit-
TG system. Some discrepancies result from different
methodical approaches as the time and the strength of
exposure of the external factor in different studies varied
wide enough, and the groups were hardly comparable by
real conditions of living. It is also mentioned that several
studies were conducted in the geographical areas in
which seasonal temperature decrease below zero was
rare, so that the examined subjects were insufficiently
exposed to cold.
The aim of this research was to study the state of the
human Pit-TG system in homogeneous group under the
conditions of chronic cold exposures during the year.
2. MATE RIALS AND METHODS
2.1. Subjects
Nineteen healthy male Caucasian volunteers (18 - 21
years) were recruited for the present annual study. The
subjects were the soldiers (military guards) in Northern
European regions of Russia (Syktyvkar, Russia, 62ºN)
that daily spent outdoors from 6 to 10 h. All the subjects
were screened by military physical and physiological
manners. The daily routine of the examined subjects was
stable throughout the observation period. The subjects
passed medical examination and were free of any dis-
eases and disorders possibly affecting their ability to
participate in study. The subjects were similar in age and
body mass index (BMI). All the recruited persons were
not obese (BMI < 30) and have been in the military unit
from 4 to 6 months-the time need for acclimations to the
North [16]. The study was approved by Institutional Re-
view Boards and each subject signed a written consent
prior to participation.
2.2. Study Protocol
The study was conducted over a 12 monthly period. The
examinations were carried out from Monday to Friday in
3-th decade of each month. The first examination was
conducted in November 2004 and the last in October
2005. The subjects woke up at 06:00 a.m. and visited a
nurse’s office at 06:30 - 07:30 a.m. Fasting blood sam-
ples were obtained from the antecubital vein into vacu-
tainer (Becton Dickinson BP) and physiological meas-
urements were performed. Blood samples were centri-
fuged and serum was placed into eppendorf microcen-
trifuge tubes and was stored at 20 until analyses.
Daily mean temperature was obtained from the Province
Meteorological Office.
2.3. Anthropometric Measurements
Body weight and height were measured using standard
medical scale and anthropometer. BMI was determined
as the ratio of body weight to height in meters squared
(kg·m2). Waist Circumference was measured to the
nearest 0.1 cm at the umbilicus level and Hip Circum-
ference was measured to the nearest 0.1 cm at the mid-
point between the greater trochanter and the top of the
patella.
The percentage of body fat mass was assessed ac-
cording to the equations of Durnin and Wommersley
[19]. For that purpose the skinfold thickness at four sites
-biceps, triceps, subscapular and suprailiac—was deter-
mined using a Scinfold caliper. The skinfold thickness
was measured three times to the nearest 0.2 mm. If result
deviated more than 1.0 mm, the three measurements
were repeated. Absolute and percent lean body mass
(LBN) were calculated from body fat mass (%) and body
weight (kg):
LBM (%) = [100—body fat mass (%)],
LBM (kg) = [weight * LBM (%)/100]
2.4. Biochemical Measurement
Serum hormones concentration was determined by en-
zyme-linked assay with a “Power Wave 200” spectro-
photometer (Bio-Tek Instruments, USA) using commer-
cial kits according to the manufactures instructions. The
reference ranges of normal values and conversion to SI
units used for these assays are: TT4 64.4 - 148.0 nmol/l
(nmol/l × 0.078 = μg/dl), FT4 10.3 - 25.7 pmol/l (pmol/l
× 0.078 = ng/dl), TT3 1.2 - 3.0 nmol/l (nmol/l × 0.651 =
ng/ml), FT3 2.1 - 6.5 pmol/l (pmol/l × 0.651 = pg/ml),
TSH 0.23 - 3.4 μIU/ml respectively.
The concentration of serum TT4 was measured by
commercial kits Randox Laboratories United Kingdom
Cat. No TX 2112 with an intraassay coefficient of vari-
ance (CV) of 8%.
The concentration of serum TT3 was measured by
commercial kits T3-total-IFA-BEST, Vector-Best, Russia,
Cat. No X-3954 with an intraassay CV of 8% and assay
detection limit of 0.2 nmol/l.
The concentration of serum FT3 was measured by
commercial kits Diagnostic Automation, Inc., Calabasas,
CA, USA, Product Code 3148 with an intraassay CV of
5.2% and assay detection limit of 0.05 pg/ml.
The concentration of serum FT4 was measured by
commercial kits Randox Laboratories United Kingdom
Cat. No FT 2137 with an intraassay CV of 8%.
The concentration of serum TSH was measured by
commercial kits Tiroid-IFA-TSH-1, Alcor Bio, Russia
with an intraassay CV 8% and assay detection limit of
0.05 μIU/ml.
E. Bojko et al. / J. Biomedical Science and Engineering 4 (2011) 462-471
Copyright © 2011 SciRes. JBiSE
464
2.5. Statistical Analysis
Data were analyzed with Statistica 6.0 (Statsoft, Tulsa,
USA). Descriptive statistics was used to calculate mean
and standard deviation (SD). Differences in annual dy-
namics of each parameter were tested by Friedman
ANOVA. Where Friedman ANOVA revealed significant
effect, a Wilcoxon test with Bonferroni correction for
multiple comparisons was used to discern differences
between months. Data in the figures and tables are pre-
sent as mean and SD.
The accepted level of significance was P < 0.05.
3. RESULTS
The outdoor air temperature at 6 a.m. characterizing the
weather during the study is presented in Figure 1.
3.1. Anthropometric Characteristics
The anthropometric characteristics of the examined sub-
jects are shown in Table 1. No significant changes in
subjects’ height and body weight were occurred over the
observation period.
3.2. Thyr o id Hormones Measure ments
The serum TSH level at the first examination in No-
vember was (1.11 ± 0.42) µIU/ml and was invariable in
December-January (Figure 2). The TSH concentration in
the examined group at the first observation varied within
normal range from 0.47 µIU/m to 2.09 µIU/m. The TSH
level was the highest in February when the concentration
of this hormone elevated significantly (P < 0.05) and
-20
-15
-10
-5
0
5
10
15
20
November
December
January
February
March
April
May
June
July
August
September
October
t,
0
C
Figure 1. The outdoor air temperature at 6 a.m. during the study.
Figure 2. The concentration of TSH in blood serum of northern European male residents during year. The vertical arrow indi-
cates the normative values of TSH (0.23 - 3.4 µIU/ml). Data are presented as mean ± SD. *P < 0.05, **P < 0.01, ***P < 0.001
compared to previous month.
*
****
***
**
0.20
0.60
1.00
1.40
1.80
2.20
2.60
3.00
November
December
January
February
March
April
May
June
July
August
September
October
TSH, µIU/ml
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E. Bojko et al. / J. Biomedical Science and Engineering 4 (2011) 462-471
Copyright © 2011 SciRes. JBiSE
466
reached (1.54 ± 0.85) µIU/ml. Next two months the TSH
level decreased consecutively and was the lowest in
April at (0.64 ± 0.18) µIU/m that was significantly lower
than during the other months. The next examination
performed in May demonstrated an increase in the TSH
level to (1.24 ± 0.32) µIU/ml (P < 0.001). In period of
May-September, the TSH concentrations were accorded
to levels observed in the subjects in November-January.
In October, the TSH level elevated to (1.45 ± 0.53) µIU/ml
(P < 0.01). The range of TSH concentrations in March-
October was 0.39 - 2.61 µIU/m.
The TT3 concentration in the subjects at the first ex-
amination was (1.45 ± 0.69) nmol/l and ranged within
limits of 0.71 - 2.93 nmol/l. In December, this parameters
increased (P < 0.01, Figure 3) and was the highest for all
observations. In February, the TT3 level decreased slightly
while that reduced extremely in March and approached
the lowest level of (1.11 ± 0.49) nmol/l in April. In May,
the TT3 level was returned back to initial values and was
stabile up to September. In October, the TT3 concentration
decreased to (1.17 ± 0.41) nmol/l (P < 0.01).
The FT3 concentration was (4.46 ± 1.21) pmol/l at the
first examination in November and (4.68 ± 1.07) pmol/l
at the last that in October (Figure 4). The FT3 level
fluctuated insignificantly within limits from 4.15 pmol/l
to 4.79 pmol/l over the year.
The TT4 level in the subjects at the first examination
was (68.2 ± 17.7) nmol/l with range of 41.9 - 89.4 nmol/l
(Figure 5). During the next eleven examinations, the
TT4 concentration fluctuated in narrow range from (62.3
± 16.5) nmol/l in March to (91.0 ± 27.64) nmol/l in Au-
gust. Seasonal dynamics of the TT4 level are given in
more detail in Figure 5.
The FT4 level in the subject group in November was
(23.2 ± 5.4) pmol/l and ranged from 13.3 pmol/l to 33.4
pmol/l (Figure 6). In November-March, the FT4 level
changed slowly. The FT4 concentration in April in-
creased significantly (P < 0.001) approaching (28.9 ±
4.0) pmol/l, and individual data ranged within limits of
18.6 - 32.0 pmol/l. This FT4 level was higher than nor-
mal range proposed by manufacturer to this hormone.
The following examinations showed that this elevated
level of FT4 remained unchanged in May-October.
4. DISCUSSION
The present study demonstrates that long-term influence
of cold air results in formation of the adaptive response
of the Pit-TG system. Our results indicate that the
chronic effect of low temperatures on human organ-
ism(guard service) is accompanied by activation of the
TH metabolism. It is necessary to noted that this activa-
tion caused by the cold influence during most part of the
year results in accumulation of FТ3 and FТ4.
Reed et al. have concluded [20] that in the euthyroid
subjects (41 years and older) in condition of prolonged
Antarctic residence, the increase in the serum TSH level
(approximately 30%) was observed without change of
the T4 concentration during the winter months. While in
the young euthyroid subjects (age 19 to 41), there was
no circannual pattern in the TSH or T4 levels but the
increase in the plasma T3 clearance rate and production
rate (approximately 30%) was revealed during winter
Figure 3. The concentration of TT3 in blood serum of northern European male residents during year. The vertical arrow indi-
cates the normative values of TT3 (1.2 - 3.0 nM/l). Data are presented as mean ± SD. *P < 0.05, **P < 0.01 compared to previ-
ous month.
**
*
**
0.20
0.60
1.00
1.40
1.80
2.20
2.60
3.00
3.40
3.80
November
December
January
February
March
April
May
June
July
August
September
October
TT
3
, nM/L
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Copyright © 2011 SciRes. JBiSE
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1.00
2.00
3.00
4.00
5.00
6.00
7.00
November
December
January
February
March
April
May
June
July
August
September
October
FT
3
, pM/L
Figure 4. The concentration of FT3 in blood serum of northern European male residents during year. The vertical arrow indi-
cates the normative values of FT3 (2.1 - 6.5 pM/l). Data are presented as mean ± SD.
Figure 5. The concentration of TT4 in blood serum of northern European male residents during year. The vertical arrow indi-
cates the normative values of TT4 (64.4 - 148 nM/l). Data are presented as mean ± SD. *P < 0.05, **P < 0.01 compared to
previous month.
Figure 6. The concentration of FT4 in blood serum of northern European male residents during year. The vertical arrow indi-
cates the normative values of FT4 (10.3 - 25.7 pM/l). Data are presented as mean ± SD. *P < 0.05, ***P < 0.001 compared to
previous month.
***
*
6.0
10.0
14.0
18.0
22.0
26.0
30.0
34.0
November
December
January
February
March
April
May
June
July
August
September
October
FT
4
, pM/L
**
*
*
*
40
60
80
100
120
140
160
November
December
January
February
March
April
May
June
July
August
September
October
TT
4
, nM/L
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Copyright © 2011 SciRes. JBiSE
468
seasons. Young subjects living in Antarctica more than 5
months had a decline in the serum T3 and T4 levels, and
the increase in the T3 clearance and production rate. Au-
thors have supposed that the T3 kinetic changes have
seasonal dependence, and the cold exposure provides
this mechanism.
To comment these results, it is to be noted that the re-
searches of inhabitants of the North have shown that the
total tension of endocrine system and the impairment of
metabolism were found during the first 6 months after
arrival in circumpolar regions [16]. Therefore, the ex-
amined group in our research consisted of subjects living
on the North no less than 6 months.
Data of Indian Antarctic expedition have shown that
the levels of total and free fractions of TH varied during
wintering. At the end of the Antarctic summer in March,
the TT3 concentrations were found to be significantly
lower (P < 0.01) compared to values recorded before
wintering and showed the significant increase (P < 0.05)
during the Antarctic winter. The TT3 levels from May to
December were found to be significantly higher than the
March or April values. The plasma TT4 concentrations
remained unaltered during wintering in Antarctica. The
FT4, FT3 levels did not show any appreciable change.
Though, the TT3:TT4 ratio tended to decline in March
and April suggesting decreased peripheral conversion of
T4 to T3 as the possible mechanism for a decline of TT3
level in March. While the monthly studies did not reveal
changes in the FT3 and FT4 levels during wintering, the
authors have suggested that the serum TH levels during
Antarctic wintering were affected by various factors of
which the physical activity and the sharp change of day
duration were the most significant. The TSH concentra-
tions in March, April, November and December were
found to be significantly higher than before wintering
[21]. These data testify on our opinion about an impor-
tant role of ethnic origin of the examined groups.
Thus, our results indicating the increase of use and
excretion of T3 in condition of long-term cold exposure
correspond to data of Reed et al. [12] and Hassi et al.
[14]. At the same time, it is to be noted that our data
show that the TT3 and TT4 levels varied insignificantly
near lower limit of norm at different temperature re-
gimes during the year. This confirms active conversion
of the connected forms of hormones to the active forms
at long stay outdoors in the North during the year.
Moreover, our results indicate that the produced stimulus
did not cause tension in the central component of the
Pit-TG system despite of activation of conversion of TH
in the free forms. This is shown by the steadily low level
of TSH and testifies that the feedback mechanism is in-
active.
In research conducted on the similar examined group
in Alaska, the essential seasonal variations of the TH
concentration were described in the infantry soldiers
during different seasons of the year [22]. The TT3 and
TT4 levels were the highest in winter while the FT3 and
FT4 levels were the highest in early spring. The correla-
tion between melatonin and T3 was revealed in spring
(light period of year). The seasonal distinctions were
also shown between indigenous and newly arrived peo-
ple, which may be related not only to cold acclimation
but also to day duration. At the same time, this examined
group was more heterogeneous in ethnic structure, time
spent in the North and professional work than our group,
which in the certain degree explains the results received
by authors. In another study, the decrease (on 20%) in
the serum FT3 level to the 76th day was shown in young
military men in Alaska during three monthly field opera-
tions [23].
In our study, the temperature of air in February has
gone down below 15, which was accompanied by
slight increase of the TSH level that testified about in-
volving of the central mechanisms of regulation. At the
same time, the content of TG peripheral hormones both
total and free form was almost unchanged. These two
facts, slight increase of the TSH concentration and the
stable level of TH in condition of accumulation of free
forms of hormones, testify in our opinion that the formed
adaptive hormonal profile was still sufficient for com-
pensation of external influence due to accumulation of
active forms of hormones.
At the same time, the increase of the TSH level in this
period is an adaptive reaction on complex of external
influences. In Leppaluoto’s opinion [4], the decrease of
the body core temperature more than on 1 causes the
TSH release. It is possible to suggest that the decrease of
air temperature below 15 and the long stay of our
examined group in these conditions are a critical level
followed by the reaction of the central component of the
Pit-TG system. Thus, the central stimulus for activation
of the TH production is formed. However, the activation
of the TH formation in the examined subjects at this pe-
riod was not observed. It is possible to suppose some
reasons for explanation of observed phenomenon. Firstly,
the decrease of air temperature occurred gradually and
the gradient of this influence was possibly insufficient
for realization of mechanisms of TH synthesis activation
in the TG. Secondly, the cold effects may reduce effi-
ciency of TH action forming relative resistance to TH
effects in tissues. It is known that actions of TH are de-
termined by intracellular concentration of free hormones.
It was demonstrated that the cytosolic T3-binding pro-
teins from human red blood cells rapidly lost activity at
low temperature [24]. Moreover, it is necessary to con-
sider that the role of cellular transport in modulating
E. Bojko et al. / J. Biomedical Science and Engineering 4 (2011) 462-471
Copyright © 2011 SciRes. JBiSE
469
intracellular concentration of TH has still been poorly
understood but the TH extrusion which can modulate
availability and action of TH in mammalian cells has
been described [25]. It has been demonstrated that tem-
perature-sensitive TH efflux mechanism that may con-
trol cellular TH-content and TH responsiveness pre-
sumably by modulating access of TH to its nuclear re-
ceptors is presented in mammalian cells. The altered
hormone transport represents one potential explanation
for hormone resistance syndromes. So the active hor-
mone efflux constitutes a novel mechanism for physiol-
ogic regulation of TH action that act through the nuclear
hormone receptor.
There are data about interrelation of the thyroid func-
tion level and the food status. It has been shown that
there is significant correlation between the Т3 and Т4
levels and the actual food consumption in Evenki, abo-
riginals of Siberia [26]. The interrelation between the
serum Т4 concentration and the daily consumption of
protein and fat was especially strong. The Т3 level posi-
tively correlated with the fatless weight of body and
negatively correlated with fatty weight of body in the
examined subjects. It has also been noted that there was
interrelation between the TH concentration, especially
with Т4, and body weight in the examined subjects. Au-
thors consider that the received results testify about in-
terrelation between the thyroid function parameters and
the basal metabolism level in aboriginals of the North
and also reflect importance of account of role of food
factor in estimation of basal level of metabolism in nor-
therners.
The study of inhabitants of northern Norway has
shown that the TSH level positively correlated with BMI
in non-smoking inhabitants whereas there was no this
correlation in smokers [27]. In our research, the BMI
parameters remained stable during most part of the year.
It is possible to note that the significant increase of the
air temperature in March-April was accompanied by the
decrease in the TSH level to minimal values found for
all time of observation. This can confirm supposition
that the TSH increase has been caused by the tempera-
ture factor. At the same time, the TT3 level decreased to
minimal values in March-April, and the TT4 concentra-
tion also reduced in March though the level of free forms
of hormones was stably high. Thus, the reduction of ex-
ternal cold influences is accompanied by decrease of
activity of the central component of the Pit-TG system,
which affects in the certain degree secretion of the TG
hormones. The mechanisms providing accumulation of
free forms of hormones are maintained. Moreover in
April, the FT4 concentration exceeded the normal level.
When the air temperature in May increased considerably
(by 25 concerning March), the TSH level came back
to January value (preceding significant increase of the
TSH level). Simultaneously, the TT3 concentration rose
insufficiently from the minimal annual levels. At the
same time, the increased FT4 level (above the normal
values) in the examined subjects was kept up to Sep-
tember. In October, the FT4 parameters returned to norm.
It is interesting to note that the hormone profile in Octo-
ber (the last month of the research) was similar to that in
February. In this time, the air temperature approached 0
that might be a critical value characterizing the ter-
mination of the warm period of year. This allows to
propose that the mechanism described by us is typical
enough for conditions of Arctic region where the envi-
ronment conditions and the temperature factor alter crit-
ically twice during the year. The similar mechanism
could be characterized as a certain “medium-term reac-
tion” so far as the accumulation of external factor effect
is required for change of functional state of separate
components of the Pit-TG system in conditions of aspi-
ration of this system to preservation of stability.
There is a supposition that the cold exposure may en-
hance the T3 production by deiodisation of T4 in skeletal
muscle via change in muscle fiber type, which could
explain the high level of T4 in the examined subjects in
summer [2]. Moreover, we should not exclude possibil-
ity that the increase of the FT4 level was caused by the
fact that the air temperature was low (from +10 to
+15) even in summer. This conditioned the formation
of TH active forms as FT3 level was stably high.
The study has shown that the long-term cold expo-
sures result in activation of use of TH active forms-FТ3
and FТ4. The change of action intensity of temperature
factor can cause acceleration of conversion of total
forms of TH in free forms of that. This process is ac-
companied by the decrease of levels of connected forms
of hormones to lower limit of norm and the accumula-
tion of FТ3 and FТ4 in blood serum to higher limit of
norm. Under these conditions, the central component of
the Pit-TG system is not activated keeping constancy of
functional state. The activation of the central component
of the Pit-TG system is occurred when influence of cold
stimulus exceeds a certain limit. This activation is shown
by increase of the level of serum TSH. The decrease of
cold factor influence intensity results in reduction of
tension of the central component of the Pit-TG system
and lowing of the serum TSH level.
It is necessary to note specially that mean parameters
of the FT3 in our examined group varied from (4.15 ±
0.91) pmol/L in June to (4.79 ± 0.69) pmol/L in December.
These results completely correspond to data obtained
Hassi et al. [14] in the annual research of young outdoor
workers from northern Finland. While our data on the
FT4 level, which varied from (21.4 ± 4.3) pmol/L to
E. Bojko et al. / J. Biomedical Science and Engineering 4 (2011) 462-471
Copyright © 2011 SciRes. JBiSE
470
(28.9 ± 4.0) pmol/l, do not conform to data of Hassi et al.
that FT4 level averaged 15 pmol/L. This is probably
caused by the fact that determination of both FT3 and
FT4 in our and above-mentioned studies was performed
by various methods and reagents of different producer
therefore there could be diverse reference ranges. De-
spite in both studies, the levels of free forms of hor-
mones were high and accorded height limit of norm.
In report of Hassi et al. [14], the important fact show-
ing significant elevation of the TSH content during pe-
riod of the minimal temperatures observed in northern
Finland in December has been described. In our research,
the TSH level also raised significantly at achievement of
the minimally low temperatures that were in conditions
of our region in February. Thus, these data also confirm
the phenomenon described earlier and allow to explain
its origin that was not possible to make in the above-
mentioned report.
5. CONCLUSIONS
Thus, the central and peripheral components of the Pit-
TG system can show certain plasticity in conditions of
long-term exposure of cold air. The results of our re-
search allowed to show that adequate selection of the
examined groups is important for revealing effect of
external long-term stimulus on human organism as it
defines obtained results. Our materials allow differenti-
ating the adaptive response of the Pit-TG system as a
whole on chronic cold air exposure showing activation
of Т3 and Т4 active forms use at the “moderate” intensity
of the external factor action. The central component of
the Pit-TG system is activated in conditions of excess of
a certain limit-excess of exposure doze. In conditions of
the North, this activation of the central mechanisms can
not cause mediated reaction from peripheral target or-
gans, and a certain resistance to ТSH effect in the TG is
observed.
REFERENCES
[1] Leblond, C.P. and Gross, J. (1943) Effect of thyroidectomy
on resistance to low environmental temperature. Endocri-
nology, 33, 155-160.
doi:10.1210/endo-33-3-1 55
[2] Laurberg, P., Andersen, S. and Karmisholt, J. (2005) Cold
adaptation and thyroid hormone metabolism. Hormone
and Metabolic Research , 37, 545-549.
doi:10.1055/s-20 05-8704 20
[3] Silvestri, E., Schiavo, L., Lombardi, A. and Goglia, F.
(2005) Thyroid hormones as molecular determinants of
thermogenesis. Acta Physiologica Scandinavica, 184, 265-
283. doi:10.1111/ j.1365- 201 X.200 5.0146 3.x
[4] Leppaluoto, J., Korhonen, I., Huttunen, P. and Hassi, J.
(1988) Serum levels of thyroid and adrenal hormones, tes-
tosterone, TSH, LH, GH and prolactin in men after 2-h
stay in a cold room. Acta Physiologica Scandinavica, 132,
543-548. doi:10.1111/j.1748-1716.1988.tb08363.x
[5] Thomas, J.R., Ahlers, S.T., House, J.F., Schrot, J., Van
Orden, K.F., Winsborough, M.M., Hesslink, R.L.Jr. and
Lewis, S.B. (1990) Adrenergic responses to cognitive ac-
tivity in a cold environment. Journal of Applied Physiol-
ogy, 68, 962-966.
[6] Leppaluoto, J., Paakonen, T., Korhonen, I. and Hassi, J.
(2005) Pituitary and autonomic responses to cold expo-
sures in man. Acta Physiologica Scandinavica, 184, 255-
264. doi:10.1111/ j.1365- 201 X.200 5.0146 4.x
[7] Leppaluoto, J., Lybeck, H., Virkkunen, P., Partanen, J. and
Ranta, T. (1982) Effects of immersion in cold water on the
plasma ACTH, GH, LH, and TSH concentrations in man.
Circumpolar Health, 81, 601-602.
[8] Hesslink, R.L.Jr., D’Alessandro, M.M., Armstrong, D.W.
and Reed, H.L. (1992) Human cold air habituation is in-
dependent of thyroxine and thyrotropin. Journal of Applied
Physiology, 72, 2134-2139.
[9] Savourey, G., Caravel, J.P., Barnavol, B. and Bittel, J.H.
(1994) Thyroid hormone changes in cold air environment
after local cold acclimation. Journal of Applied P hysiol ogy,
76, 1963-1967.
[10] Nagata, H., Izumiyama, T., Kamata, K., Kono, S. and Yu-
kimura, Y. (1976) An increase of plasma triiodothyronine
concentration in man in cold environment. Journal of
Clinical Endocrinology and Metabolism, 43, 1153-1156.
doi:10.1210/jcem-43-5-1153
[11] Reed, H.L., Fereiro, J.A., Shakir, K.M., Burman, K.D. and
O`Brain, J.T. (1988) Pituitary and peripheral hormone re-
sponses to T3 administration during Antarctic residence.
American Journal of Physiology: Endocrinology and Me-
tabolism, 254, E733-739.
[12] Reed, H.L., Reedy, K.R., Palinkas, L.A., Van Do, N., Fin-
ney, N.S., Case, H.S., LeMar, H.J., Wright, J. and Thomas,
J. (2001) Impairment in cognitive and exercise perform-
ance during prolonced Antarctic residence effect of thy-
roxine supplementation in the polar triiodthyronine syn-
drome. Journal o f Clinical En docrinology and Met abolism,
86, 110-116. doi:10.1210/jc.86.1.110
[13] Harrop, J.S., Ashwell, K. and Hopton, M.R. (1985) Cir-
canual and within-individual variation of thyroid function
tests in normal subjects. Annals of Clinical Biochemistry,
22, 371-375.
[14] Hassi, J., Sikkila, K., Ruokohen, A. and Leppaluoto, J.
(2001) The pituitary-thyroid axis in healthy men living
under subarctic climatological conditions. Journal of En-
docrinology, 169, 195-203.
doi:10.1677/joe.0.1690195
[15] Leppaluoto, J., Sikkila, K. and Hassi, J. (1998) Seasonal
variation of serum TSH and thyroid hormones in males
living in Subarctic environmental conditions. International
Journal of Cir cumpolar Health, 57, 383-385.
[16] Boiko, E.R. (1996) Realignment of human metabolism in
the North. Human Physiology, 22, 496-502.
[17] Bojko, E.R. (1997) Metabolic changes induced by adapta-
tion at 78 degrees North: Svalbard study. International
Journal of Cir cumpolar Health, 56, 134-141.
[18] Boiko, E.R., Bichkaeva, F.A., Tkachev, A.V. and Dogadin,
S.A. (1997) Regulation of metabolic reactions in various
groups of aboriginal people of Polar Europe: an example
of loading test with thyrotropin-releasing hormone. Human
E. Bojko et al. / J. Biomedical Science and Engineering 4 (2011) 462-471
Copyright © 2011 SciRes. JBiSE
471
Physiology, 23, 469-471.
[19] Durnin, J.V. and Wommersley, I. (1974) Body fat assessed
from total body density and its estimation from skinfold
thickness measurements on 481 men and women aged
from 16-72 years. British Journal of Nutrition, 32, 77-97.
doi:10.1079/BJN1974006 0
[20] Reed, H.L. (1995) Circannual changes in thyroid hormone
physiology: the role of cold environmental temperatures.
Arctic Medical Research , 54, 9-15.
[21] Sawhney, R.C., Malhotra, A.S., Nair, C.S., Bajaj, A.C.,
Rajan, K.C., Pal, K., Prasad, R. and Basu, M. (1995) Thy-
roid function during a prolonged stay in Antarctica. Euro-
pean Journal of Applied Physiology and Occupational
Physiology, 72, 127-133.
doi:10.1007/BF00964 127c
[22] Levine, M., Duffy, L., Moore, D.C. and Matej, L.A. (1995)
Acclimation of non-indigenous sub-Arctic population:
seasonal variation in thyroid function in interior Alaska.
Comparative Biochemistry and Physiology. Part A: Com-
parative Physiology, 111, 209-214.
doi:10.1016/0300-9629( 95)0 001 6-Z
[23] McCormack, P.D., Thomas, J., Malik, M. and Staschen,
C.M. (1998) Cold stress, reverse T3 and lymphocyte func-
tion. Alaska Medicine, 40, 55-62.
[24] Fanjul, A.N. and Farias, R.N. (1993) Molecular intercon-
version of cold-sensitive cytosolic 3,3’,5-tri-iodo-lthyronine-
binding proteins from human erythrocytes: effect of cold,
heat and pH treatments. Biochemical Journal, 290, 579-
582.
[25] Ribeiro, R.C., Cavalieri, R.R., Lomri, N., Rahmaouli,
C.M., Baxter, J.D. and Scharschmidt, B.F. (1996) Thyroid
hormone export regulates cellular hormone content and re-
sponse. Journal of Biological Chemistry, 271, 17147-
17151. doi:10.1074/jbc.271.29.17147
[26] Leonard, W.R., Galloway, V.A., Ivakine, E., Osipova, L.
and Kazakovtseva, M. (1999) Nutrition, thyroid function
and basal metabolism of the Evenki of central Siberia. In-
ternational Journal of Circumpolar Health, 58, 281-295.
[27] Nyrnes, A., Jorde, R. and Sundfjord, J. (2006) Serum
TSH is possibly associated with BMI. International
Journal of Obesity, 30, 100-105.
doi:10.1038/sj.ijo.0803112