Human Growth Hormone Secretion During Exposure to Hot Air in Normal Adult Male Subjects YOSHIAKI OKADA,* TORU MATSUOKA,** AND YUICHI KUMAHARA*** * Third Department of Medicine, Tottori University School of Medicine, Yonago, Japan, ** First Department of Medicine, Osaka University School of Medicine, Fukushima-ku, Osaka, Japan, *** Central Laboratory for Clinical Investigation, Osaka University Hospital, Fukushima-ku, Osaka, Japan overweight, although body temperature increased to 37.5 C, HGH levels showed an increment of only 1.5 ng/ml. Nonesterified fatty acids (NEFA) increased to peaks ranging 138.9-189.5% of initial values in four subjects during the exposure to heat, but varied little in one. No significant changes in values of cortisol, total thyroxineiodine, blood glucose, or hematocrit were noted during the heat exposure. The increased HGH response to hot air exposure did not occur in two subjects given oral administration of 100 g of glucose 0 and 30 min before heat exposure. (/ Clin Endocr 34: 759, 1972)

ABSTRACT. Four normal and one obese adult male subjects were exposed to hot air (48 C) for 1 hr after an overnight fast. Body temperature was elevated over 37.5 C and severe hyperhidrosis(hydrosis) with tachycardia occurred during the exposure. Body weight decreased by 0.5-1.5 kg in all subjects. In four of the subjects with normal body weight, plasma growth hormone (HGH) levels increased from less than 1.6 ng/ml to peaks ranging 6.2-30 ng/ml at 60 min after the beginning of heat exposure. HGH levels decreased to initial values within 1 hr after heat exposure was discontinued. In one subject, 2 1 %

I

T IS NOW well established that human growth hormone (HGH) secretion is stimulated by various kinds of stress (1-2), the administration of pyrogenic agents (3) and exercise (4). Increased HGH levels associated with pyrogen-induced fever appear to, in all likelihood, be secondary to the administered pyrogen since pyrogen in the absence of measured temperature elevation is associated with HGH release (5). Innoculation of human subjects with sand fly virus was associated with a significant HGH rise in normal volunteers prior to the appearance of fever associated with that illness (6). Conversely, however, HGH levels have been noted to rise in subjects, who have been exposed to cold, on rewarming (7). Because of uncertainties as to the specific contribution of body temperature elevation to the release of HGH, it was deemed worthwhile to investigate whether HGH secretion would be affected by heating the body surface and thereby raising the body temperature. The present study describes certain metabolic and hormonal changes which take place when normal subjects are exposed to hot air (48 C) in a Sauna room for 60 min. Received June 10, 1971.

Materials and Methods Four normal and one moderately obese adult male subjects (A, B, C, D and E) aged 19-45 rested comfortably in a chair for more than lhr in a 23 C air-conditioned room following an overnight fast. The subjects wore only swimming clothes and after this period of time entered a 46-48 C room (Sauna bath) by walking (3-4 steps). The humidity of the room was less than 40%. Exposure to hot air lasted for 1 hr. During this time all subjects remained seated. After the heat exposure subjects moved back into the 23 C room and remained seated for an additional hr. No fluids were allowed until termination of the study. 50 g of glucose in 200 ml of water were given to two of the subjects (C and D) at 30 and 0 min prior to a repeat test exposure to heat. Sublingual body temperature and pulse rate were measured at intervals of 30 min. Blood specimens were drawn from an anticubital vein into a heparinized syringe at intervals of 30 min starting 30 min before the heat exposure. A sample was taken for hematocrit and the remainder of the aliquot centrifuged and the plasma stored at —20 C until analyses were undertaken. Plasma HGH concentration was measured using a double antibody immunoassay procedure (8). Wilhelmi HGH (HS 1147) was used as a standard. The concentrations of NEFA, cortisol and glucose in plasma were determined by the

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36.5 ± 0.13 to 37.7 ± 0.20 C and returned to normal after the heat exposure was over. Body weight decreased by 0.5-1.5 kg in all subjects in response to the heat. Hematocrit values showed no significant change throughout the test (Table 1). Mean pulse rate increased from 72.4 ± 0.9 to 98.0 ± 2.5/min at 60 min.

23°C

23°C

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HGH. In the four non-obese subjects HGH levels increased from less than 1.6 ng/ml to a maximum ranging from 6.2-30 ng/ml at 60 min after the onset of heat exposure and then decreased to basal values (less than 3.3 ng/ml) 1 hr after the heat stress was stopped. In the one subject with moderate obesity (E), HGH levels increased from 2.0 to 3.5 ng/ml during the exposure to heat. Control studies at room temperature showed no increase in HGH levels in any of the normal subjects (Table 2).

-30

0

30

60

90

Time

120

min

FIG. 1. Change of body temperature and plasma HGH levels before and after exposure to hot air (46-48 C) for the period of 1 hr in four normal and one obese male subjects. • — • , • — D , • — • , A—A and O—O represent subjects A, B, C, D and E, respectively.

NEFA. NEFA increased to 149.5, 146.3, 187.5 and 169.3% during hot air exposure in subjects B,C,D and E, respectively, but did not change in subject A (Table 1). Cortisol. Cortisol levels changed little in any of the subjects in control studies and in three subjects (A,D and E) exposed to hot air, but increased by 9.3 and 10.4 ^g/100 ml at 120 min in subjects B and C, respectively.

methods of Dole (9), DeMoor (10) and ferricyanide reduction method using the Technicon Auto Analyzer (11), respectively. Total thyroxine-iodine was measured by using a commercial kit ((§) Tetralute). Control studies were performed on the same fasting, seated subjects at room temperature. Four subjects (A, B, C and D) were within normal limits of body weight, but one subject (E) was 2 1 % overweight.

Others. The values of blood glucose, total thyroxine-dodine, hematocrit are summarized in Table 1. No significant changes were observed. In a second experiment two subjects (C and D) received 50 g of glucose orally at 30 and 0 min prior to the onset of heat exposure. Plasma glucose levels remained greater than 126 mg/100 ml throughout the period of heat exposure. Body temperature during Results this study increased from 36.0 to 38.0 and Physical examination. Mean temperature re- 37.9 C when measured at 60 min in each of sponses of the five subjects following expos- these subjects. HGH levels, however, deuse to hot air are shown in Fig. 1. Severe creased from 1.7 to 0.5 and from 1.0 ng/ml hyperhidrosis began to take place at 20 to undetectable level at 60 min in these two min and body temperature increased from subjects (Table 3).

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HGH SECRETION IN HEAT EXPOSURE

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Discussion to hot air. It seems unlikely that HGH levels increased in response to fever since HGH response to the administration of the body temperature elevation occurred in bacterial pyrogens appears to be related to parallel with the increased HGH levels. In an effect of pyrogens per se on HGH secreour laboratory, HGH values during insulintion and is not due to the stress of fever and induced hypoglycemia, performed in 37 norsymptoms associated with body temperature mal subjects, reaches a maximum ranging elevation (5). Further support for disbelieving that fever may evoke HGH release was from 8-55 ng/ml (mean 22.4 ± 10.0 ng/ the demonstration that increased basal ml) when a Wilhelmi HGH (HS 1147) HGH levels are noted after the administra- standard is used in the assay system. Thus tion of sand fly fever virus several hr prior it would appear that the increased HGH reto the onset of fever and clinical symptoms sponse to hot air exposure is comparable to (6). Nevertheless, some effect of body tem- that obtained with insulin-induced hypoglyperature on the regulation of HGH release cemia. This HGH increase noted during heat is suggested by the demonstration that HGH exposure does not appear to be due to levels do indeed rise upon rewarming after merely a daily variation of HGH level, since exposure to cold. In the present study it control studies at room temperature showed appears that HGH secretion is also stim- no significant HGH changes. ulated when the body surface was exposed A very slight increase (1.5 ng/ml) in TABLE 1. Hematocrit, blood glucose, thyroxine-iodine, NEFA, plasma cortisol and HGH levels in four and one obese subjects before and after exposure to hot air (46-48 C) for the period of 1 hr T i m e in min Substances Hematocrit

(%)

Subjects

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0

30

60

90

120

A B C D

44 42 48 45 46

44 41 47 47 47 99

44 41 50 47 49 105

44 41 48 47 46 108 100

4.8 5.5 5.2 4.6

44 41 47 48 47 108 97 66 65 102 5.9 5.0 5.8 5.2 4.5

45 42 48 47 46 110 90 67 65 101 6.3 4.4 5.8 5.2 4.8

15.3

7.2

E Blood Glucose (mg/100 ml)

Thyroxineiodine (jig/100 ml)

Cortisol (Mg/100 ml)

NEFA (nEq/1)

HGH (ng/ml)

A B C D E A B

C D E A B C D E A B C D E A B C D E

100 96

66 64 100 5.9 4.7 5.5 5.0

4.5 20.1 12.0 19.4 20.6 19.8

577 — 290 — — 5.0 1.2 1.6 1.7 2.4

101

70 64 100

100 72

66

5.5 4.5

64 98 5.9 4.5 5.5 5.2 4.5

14.4

13.8

20.1

7.2

7.2

9.6

18.9 17.9 30.2

16.9 15.2 22.7

19.7 15.9 27.0

25.2 18.6 29.2

564 307 283 320 322 1.4 0.8 1.3 1.6 2.0

568 459 331 510 499 1.6 1.2 8.4 2.5 2.2

5.5

61 94 6.2 5.0 5.3

530 373 414 600 545 12.0

6.2 30.0 10.0

3.5

602 295 392 536 465 4.6 3.8 9.4 4.0 2.2

18.0 17.6 28.2 20.4 31.5

594 301 524 491 360

1.5 1.2 3.3 2.2 1.6

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TABLE 2. Plasma cortisol and HGH levels of control studies performed on the same fasting, seated normal subjects at room temperature Substances

Subjects

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0

Cortisol Og/100 ml)

A B C D A B C D

20.1 21.9 19.2 23.1 0.6 1.6 2.4 1.1

15.9 19.2 16.5 23.1 0.9 0.6 2.9 1.8

HGH (ng/ml)

Time in min 30 60 14.1 17.1 14.1 — 1.7 < 1.8 1.5

15.3 14.7 14.4 26.4 0.7 0.7 0.7 1.2

90

120

18.6 15.3 12.9 25.8 0.6 0.5 0.9 1.5

16.5 15.3 12.3 25.8