Effect of simulated ascent to 3500 meter on neuro-endocrine functions.

Ascent to extreme High Altitude (HA) is in steps and it entails acclimatization at moderately HA locations. In terms of acclimatization, it is pertinent to understand the physiological changes, which occur on immediate ascent to moderate HA. The study aimed to evaluate the effect of ascent to 3500 m on neuro-endocrine responses in the first hour of induction. The plasma levels of catecholamines and cortisol were measured before and after one hour of ascent to high altitude. The peripheral oxygen saturation (SpO2), Galvanic Skin Resistance (GSR), Heart Rate (HR) and Blood Pressure (BP) were simultaneously monitored. The plasma epinephrine, norepinephrine, dopamine and cortisol were increased after one-hour exposure to 3500 m altitude as compared to before exposure. The SpO2 showed a significant decrease during and after high altitude induction. The heart rate and diastolic BP increased at 3500 m whereas the GSR did not show significant changes. There are changes in neuroendocrine responses, which reflect a sympathetic over activity in the first hour of exposure to 3500 m.

Plasma insulin and growth hormone during antarctic residence.

Circulatory levels of insulin and growth hormone (GH) were estimated in nine tropical euglycemic men in New Delhi and during the first week of every month of stay in Dakshin Gangotri, Antarctica. Prolonged residency in Antarctica did not alter GH levels because mean GH values during Austral summer and Austral winter were not significantly different from the New Delhi values. Compared with GH, the insulin levels during March, April, and June were found to be significantly lower than the New Delhi values. In Antarctica, the insulin levels in March, April, May, June, July, and August were also found to be significantly lower than the December values. This decline in insulin in Antarctica might be important in increasing substrate availability for heat production by facilitating lipolysis and hepatic glucose output.

Kinetics of two different iron formulations and their effect on diurnal variation of serum iron levels.

Iron polymaltose complex (IPC) is a recently marketed preparation with questionable bioavailability. We compared the absorption kinetics of IPC with ferrous sulfate. We also studied the effect of oral iron on diurnal variation. The study was conducted in eight healthy, non-smoking, non-alcoholic volunteers after obtaining their written informed consent and after Institutional Ethical Committee approval. The study was conducted in three phases: during the first phase no drugs were given, whereas in the second and third phases, ferrous sulfate (66 mg elemental iron) and IPC (100 mg elemental iron) were given in a randomized, two-way, cross-over design, with a wash-out period of 1 week. The blood samples were collected, iron levels estimated and the pharmacokinetic parameters calculated. Circadian rhythm in iron levels was demonstrated by cosinor analysis with a mesor of 93.6 microg/dl, acrophase 10.40 h and amplitude of 26.4 microg/dl. Evening levels were higher as compared with morning levels. Drug treatment increased the mesor (115.7 microg/dl; p < 0.05), delayed the acrophase (11.30 h; p < 0.05) and increased the amplitude (38.5 microg/dl; p < 0.05). The bioavailability of ferrous sulfate was significantly greater as compared with IPC with greater Cmax and AUC (p < 0.05). A clear cut circadian rhythm in iron concentrations was demonstrated. Ferrous sulfate was shown to have significantly higher bioavailability as compared with IPC. Further studies having hemoglobin levels as an endpoint may be planned.

Circadian rhythmicity of growth hormone at high altitude in man.

Circulatory levels of growth hormone (GH) were estimated at 0600 h, 1200 h, 1800 h and 2400 h in each of 10 subjects of sea level residents (SLR) in New Delhi (226 m) and in high altitude natives (HAN) settled at an altitude of 3650 m. Both in SLR and HAN the GH secretion showed an identical pattern, the values were lowest at 0600 h and highest at 2400 h. Nevertheless, in HAN the GH levels at different timings of the day were found to be significantly higher than in SLR.

Plasma insulin, growth hormone, and blood sugar during exercise in man.

Alterations in plasma immunoreactive insulin (IRI), human growth hormone (hGH) and blood glucose were studied in five male volunteers undergoing exercise for 20 min on a bicycle ergometer at 750 kpm/min. Plasma IRI and hGH levels before exercise were 4.42 +/- 1.35 micro U/ml (mean +/- SE) and 1.94 +/- 0.88 ng/ml respectively. A significant decrease (p less than 0.01) in plasma IRI was observed at 20 min postexercise and remained at lower levels upto 80 min of observations. hGH levels showed significant increase (p less than 0.05) to a mean value of 7.46 +/- 0.71 ng/ml at 20 min of exercise with a peak value of 16.0 +/- 5.04 ng/ml at 20 min postexercise. Sixty min after termination of exercise, hGH levels returned to pre-exercise values. Blood glucose rose progressively with the increase in the duration of exercise and peak levels were recorded at 20 min of exercise. Sixty min after termination of exercise, blood glucose levels returned to pre-exercise values. These observations suggest that exercise stress can lead to a physiological situation in which circulating insulin and glucose are not exclusively dependent on each other.

A study of pituitary-thyroid function during exercise in man.

Exercise induced modulations in circulatory T4, T3 and TSH were monitored in 14 healthy euthyroid male volunteers undergoing exercise on a bicycle ergometer at 750 KPM for 20 minutes. TSH response to 100 micrograms TRH was also studied in 4 exercising and 4 resting subjects. Serial blood samples were obtained before, during and after the exercise. Serum T4 exhibited a significant decrease (P less than 0.05) from 9.6 +/- 0.49 microgram/dl (mean +/- SE) to 8.3 +/- 0.47 microgram/dl at 20 min after the termination of the exercise, whereas a significant decrease (P less than 0.01) in T3 levels from 158 +/- 9 ng/dl to 144 +/- 8.2 ng/dl was recorded at 40 min after the termination of the exercise. The basal TSH levels as well as the sensitivity of the pituitary thyroid axis, monitored as overall TSH response, reflected by the sum of TSH values at different time intervals and the maximum rise over the basal levels (delta TSH) remained unaltered after exercise. These observations suggest that hormone secretion by the thyroid and its responsiveness to endogenous TSH are maintained after exercise. The decrease in circulatory T4 and T3 could be due to an increase in degradation of the hormones or may reflect a generalized adaptation phenomenon. The exact mechanism and significance of these alterations remains to be elucidated.

Thyroid function in sojourners and acclimatised low landers at high altitude in man.

The circulatory levels of T4, T3, rT3, TSH as well as TSH response to TRH, thyroid hormone binding proteins and T3 concentration of erythrocytes were studied in (i) healthy euthyroid sea level residents (SLR) at sea level, (ii) during three weeks of stay of SLR at an altitude of 3500 m (sojourners, SJ), (iii) SLR staying at high altitude (HA) for 3 months to 10 years (acclimatised low landers. ALL), (iv) high altitude natives (HAN) and (v) euthyroid men during intermittent exposure to simulated altitude of 3500 m in a hypobaric chamber maintained at an ambient temperature of 22 degrees C to 24 degrees C. Hypoxic stress either simulated or natural, produced marked elevation in plasma T4 and T3 within 4 h and the increased levels were maintained during the entire period of exposure. The circulatory levels of T4 and T3 were higher in HAN and ALL compared to SLR values. The T3 concentration of erythrocytes was decreased (P less than 0.01) at HA, whereas plasma rT3, TBG and T4 binding capacities of TBG and TBPA did not show any appreciable change. Plasma TSH at high altitude in SJ, ALL and HAN was not significantly different from the SLR values. Furthermore, when L-eltroxine treated (L-T4, 0.5 mg/d for 11 days) euthyroid men were subjected to simulated altitude, there was an elevation in both T4 and T3 suggesting that the rise in hormone levels was independent of pituitary secretion of thyrotropin. Both T4 and T3 returned to SLR values when SJ and HAN were brought down to SL.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroid function during intermittent exposure to hypobaric hypoxia.

Circulatory levels of triiodothyronine (T3) and thyroxine (T4) and their kinetics were studied in rabbits exposed to intermittent hypobaric hypoxia (5200 m, 395 mm Hg, PO2 83 mm Hg) 6 h daily for 5 weeks in a decompression chamber maintained at room temperature of 22 degrees-24 degrees C. Kinetics of T3 and T4 were studied on days 21 and 28 of hypoxic exposure. The T3 and T4 values were found to be significantly lower on day 8 of exposure to hypoxia compared to the pre-exposure values. The decreased levels were maintained throughout the entire period of hypoxic stress. The metabolic clearance rate, production rate, distribution space and extrathyroidal T3 and T4 pools were significantly decreased in animals under hypoxic stress compared to the control animals. The decline in thyroid hormone levels and their production in rabbits under hypoxic stress indicate an adaptive phenomenon under conditions of low oxygen availability.

Glucoregulatory hormones in man at high altitude.

Concentrations of glucose, lactic acid, free fatty acid (FFA), insulin, cortisol and growth hormone (GH) in the blood were monitored in 15 euglycaemic men (sojourners, SJ) at sea level (SL) and while at altitudes of 3500 m and 5080 m, in acclimatised low landers (ALL) and in high altitude natives (HAN). In SJ, blood glucose and insulin concentrations showed a significant increase on the 3rd and 7th day after arrival at high altitude (HA), thereafter returning to sea level values and remaining the same during the entire period of their stay at 3500 m. Subsequently, on arrival at higher altitude (5080 m) the glucose concentrations again showed an increase over the preceding values and returned to SL values on day 41 while at 5080 m. A significant increase in cortisol concentrations was seen on day 3 after arrival at HA and the increased levels were maintained until day 21 at 3500 m. The cortisol concentrations on day 30 after arrival at 5080 m came down to SL values and remained unchanged thereafter. No appreciable change in GH and FFA was seen during the sojourn at HA. On the other hand, blood lactic acid concentration decreased significantly. There was no difference between the fasting glucose concentrations in ALL at 3500 m and in HAN at 3500 m and 4200 m compared to values of SJ at SL, whereas ALL at 4200 m had higher glucose values. Concentrations of plasma insulin and GH in ALL and HAN were higher than the values of SJ at SL, whereas cortisol values did not show any difference. These observations indicated that at HA the glucose values were high for the insulin concentration observed and might have been due to increased secretion of GH by the pituitary gland.

Free and total thyroid hormones in humans at extreme altitude.

Alterations in circulatory levels of total T4 (TT4), total T3 (TT3), free T4 (FT4), free T3 (FT3), thyrotropin (TSH) and T3 uptake (T3U) were studied in male and female sea-level residents (SLR) at sea level, in Armed forces personnel staying at high altitude (3750 m) for prolonged duration (acclimatized low-landers, ALL) and in high-altitude natives (HAN). Identical studies were also performed on male ALL who trekked to an extreme altitude of 5080 m and stayed at an altitude of more than 6300 m for about 6 months. The total as well as free thyroid hormones were found to be significantly higher in ALL and HAN as compared to SLR values. Both male as well as female HAN had higher levels of thyroid hormones. The rise in hormone levels in different ALL ethnic groups drawn from amongst the southern and northern parts of the country was more or less identical. In both HAN and ALL a decline in FT3 and FT4 occurred when these subjects trekked at subzero temperatures to extreme altitude of 5080 m but the levels were found to be higher in ALL who stayed at 6300 m for a prolonged duration. Plasma TSH did not show any appreciable change at lower altitudes but was found to be decreased at extreme altitude. The increase in thyroid hormones at high altitude was not due to an increase in hormone binding proteins, since T3U was found to be higher at high altitudes.(ABSTRACT TRUNCATED AT 250 WORDS)

Pituitary, gonadal and adrenal hormones after prolonged residence at extreme altitude in man.

High altitude-induced alterations in pituitary, gonadal and adrenal hormones were studied in (i) eugonadal men from the armed forces who were resident at sea level (SL), (ii) SL residents staying at an altitude of 3542 m for periods ranging from 3 to 12 months (acclimatized lowlanders, ALL), (iii) ALL who stayed at 6300 m for 6 months, (iv) ALL who trekked from 3542 to 5080 m and stayed at an altitude of more than 6300 m in the glacier region for 6 months, and (v) high-altitude natives (HAN) resident at an altitude of 3300-3700 m. Circulating levels of LH, FSH, prolactin, cortisol, testosterone, dihydrotestosterone (DHT) and progesterone in ALL at 3542 m and in HAN were not significantly different (p > 0.05) from the SL control values. When the ALL living at 3542 m trekked to an extreme altitude of 5080 m, their testosterone levels showed a significant decrease (p < 0.01) compared to the preceding altitude values but had returned to SL values when measured after 6 months' continuous stay at 6300 m. As with testosterone, the levels of DHT and oestradiol-17 beta (E2) after prolonged stay at extreme altitude were also not significantly different (p > 0.05) from the SL values. The LH levels after trekking to 5080 m were significantly higher (p < 0.01) than at an altitude of 3542 m, but decreased to levels found at 3542 m or SL after prolonged residence at extreme altitude. Plasma levels of ACTH, prolactin, FSH and cortisol on arrival at 5080 m, and after a 6-month stay at extreme altitude, were not significantly different (p > 0.05) from the SL values. Plasma progesterone levels tended to increase on arrival at 5080 m but a significant increase (p < 0.001) was evident only after a 6-month stay at extreme altitude. These observations suggest that prolonged residence at lower as well as at extreme altitude does not appreciably alter blood levels of pituitary, gonadal or adrenal hormones except for plasma levels of progesterone. The exact mechanism and significance of this increase remains unknown, but may be important in increasing the sensitivity of the hypoxic ventilatory response and activation of haemoglobin synthesis.

Hormone profiles at high altitude in man.

Altitude induced alterations in circulatory levels of PRL, LH, FSH and testosterone were studied in seven eugonadal men at sea level (SL), during their stay at high altitude (HA, 3500 m) and a week after return to SL. The mean plasma PRL level at SL was 5.83 +/- 1.7 SE ng/ml. On day one and seven of arrival at HA, the PRL values of 7.81 +/- 1.81 and 9.21 +/- 1.64 ng/ml respectively were not significantly different (p greater than 0.05) than the initial SL values. However, on day 18 of stay at HA, PRL levels were significantly increased (p less than 0.01) to 17.68 +/- 1.82 ng/ml and returned to initial SL values within seven days of return to SL. A significant decrease (p less than 0.01) in LH and testosterone was observed on seventh day of stay at HA and the decreased levels were maintained till day 18 of observations. Plasma testosterone returned to the initial SL values within a week of return to SL, whereas LH levels remained significantly lower (p less than 0.01). The FSH levels did not show any significant change during their stay at HA or after return to SL. These observations suggest that exposure to altitude is associated with hyperprolactenemia and an impaired pituitary gonadal function. The decreased levels of LH and testosterone at HA could either be due to hypoxic stress per se or secondary to altitude induced hyperprolactenemia.

Pituitary-gonadal hormones during prolonged residency in Antarctica.

Plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL) and testosterone levels were measured in nine eugonadal men in New Delhi and during the 1st week of different months of their stay at Dakshin Gangotri in Antarctica. During their 12-month stay in Antarctica, they were exposed to a severely cold climate, long polar nights and polar days, high wind velocity, increased amounts of solar and ultraviolet radiation and geomagnetism, as well as physical and social isolation. Plasma testosterone tended to increase in March, but a significant increase (P < 0.05) was not seen until April. The mean testosterone levels in May, June, September and November were also significantly higher than the March or New Delhi values. The absolute values of LH, FSH and PRL did not show any month-to-month changes in Antarctica. However, when the hormone levels were expressed as a percentage of the individual annual Antarctic mean, significant differences as a percentage of the individual annual Antarctic mean, significant differences were observed. The testosterone peak in April, May and June was associated with an increase in LH. The nadirs of testosterone, LH, FSH and PRL were seen in either July or August. FSH showed the highest values in March, whereas the highest PRL values were seen in November. These observations suggest the presence of circannual variations in gonadotropin, PRL and LH in Antarctica which are independent of polar days and polar nights. It appears that factors other than the duration of daylight might be involved in regulating these changes. The significance of maintenance of testosterone levels in the supra-physiological range in Antarctica remains unknown but may be important in acclimatization/habituation to the extreme polar cold by increasing basal metabolic rate, protein synthesis and erythropoiesis.

Thyroid function during a prolonged stay in Antarctica.

Adaptation of the thyroid gland to the Antarctic environment was studied in nine healthy euthyroid tropical men of the Sixth Indian Antarctic Expedition during 1 year of their residence at polar latitudes. Circulatory concentrations of thyroid hormones, total T4 (TT4), total T3 (TT3), free T4 (FT4), free T3 (FT3), reverse T3 (rT3), thyroxine binding globulin (TBG), T3 uptake and thyroid stimulating hormone (TSH) were estimated in New Delhi and during the first week of each month of the stay in Antarctica. At the end of the Austral summer in March, the TT3 concentrations were found to be significantly lower (P < 0.01) compared to values recorded in New Delhi and showed a significant increase (P < 0.05) during the Austral winter in August. The mean TT3 concentrations from May to December were found to be significantly higher than the March or April values. Plasma TT4 and rT3 concentrations tended to decline in March but remained unaltered during the entire period in Antarctica. The FT4, FT3, TBG and T3 uptake 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 in TT3 in March. physical exertion and prolonged exposure to extreme cold appeared to be the major contributory factors. The TSH concentration in March, April, November and December were found to be significantly higher than the New Delhi values. The morning as well as evening cortisol concentrations during the Austral winter were higher than the March values suggesting that cortisol rhythmicity was well maintained in Antarctica, albeit at a higher level. These observations indicated that the subtle changes in thyroid hormones during a prolonged stay at polar latitudes are related not only to the extreme cold but also to other factors such as physical activity, polar days and polar nights.