The effect of heat stress on body development in rats

Lüe Scienc Vol . 9, Part I, pp . 1191-1200, 1970. Printed in Great Britain

Pergamon Press

THE EFFECT OF HEAT STRESS ON BODY DEVELOPMENT IN RATS S. Dikstein, Y. Kaplanski, Y. Koch and F. G. Sulman Department of Applied Pharmacology, School of Pharmacy, Hebrew University, Jerusalem, Israel

(Received 18 May 1970; is ünal form 9 September 1970) IN an earlier publicationl we studied the normal development of rats during the decisive phase o! their maturation, the 21st to 42nd day of life .

With the

aid of a computer, standards for normal growth, sexual maturity and organ weights were established.

The standard values obtained for normal developg-10 and

ment allowed us to assess the effect of hormones 2-5, drugs starvationl.

The effect on the pineal glandll was similarly studied.

The present publication deals with the effect of dry heat on body development of rata, showing that real heat stress only occurs at temperatures exceeding 34~C .

Materials and Methods A 'feat room" for animals was installed for this research, making it possible to simulate hot climates ranging between 28-38~C (± 1~C) at a relative humidity (RH) of 20-40°0 .

The contrdl animals were kept in a

parallel room at a temperature of 23 (} 1)~C with a RH of 50-80yó .

Fluorescent light was automatically switched on and off at 12-hourly intervals.

Groups of 6 rata ("Sabra" Hebrew University strain) of both

sexes were reared separately at different seasons in both rooms on standard lood at varying temperatures .

Initial body weight of the rats was 40 t 5 g

for the females and 45 ± 5 g Por the males.

The period of assag lasted from

the 21st to the 42nd day of age, i. e . the most decisive phase of maturation. Food and water were given ad libitum, with the ezception of the

experiment in which paired Peedìng was used .

1191

The normal food intake was

1192

EFFECT OF HEAT STRE33

14 g/day;

Vol. 9, No. 20

water intake varied, especially with increasing temperatures .

The food pellets contained : proteins 25 . 5g'o, cellulose 4. nitrogen-free extract 49 .3°90, bentonite 2gó, water 11°90,

8°Jo,

fat 2 .2 °Jo,

mineral ashes 5 .2~o and

Placing of the rat cages and temperature measurements took into account the hazards of air circulation and adequate needs of bedding for nest building .

The rata were inspected once daily for general behavior

and sexual development, especially spontaneous opening of the vagina testicle descent.

17-KS were assayed by the method of Sulman l2 .

or

The

tibia test was performed as described by us . 13 On the 42nd day all rats were killed and the organs dissected, cleaned and weighed after blotting with filter paper in the following order, to avoid the risk of drying of the organs during dissection : (without the isthmus), kidneys and liver.

adrenals,

genital tract,

thyroid

thymus, heart,

spleen,

The results were fed into an IBM 7040 computer and

a student t-Test was performed.

No seasonal differences could be

discerned .

Results A.

Development at Unlimited Food Intake The results of heat stress in maturing rats are compiled in

Tables 1 and 2.

Each column represents the figures obtained from

three repeat series carried out at different seasons on 8 rats each . The optimal temperature, for body growth, was 28-28~C at 40% RH . The threshold temperatures at which decisive changes were recorded ranged between 30° and 34°C at 20-40% RH .

At 38°G (the near-fatal

temperature) extreme stress reactions were obtained which will be considered separately.

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1) Reari ng at 30-34~C The main findings between 30" and 34~C (20-30"Jo RH) were ae follows"

Body weight was reduced by up to 12y6 in females, and 10°Jo in males.

Kidney

weight was reduced significantly in females, but not in males . Thyroid weight was reduced by up to 35°Jo in females and 30yó in males.

Adrenal

weight was not affected in either the females or males, nor were thymus weight, heart, spleen or liver.

Sexual development was significantly accelerated in females : vaginal

opening was up to 5 days earlier than in controls, ovarian weights increased considerably, due to swollen follicles and corpora lutes, with the number of the latter nearly doubled.

Sexual development was less conspicuously accelerated in males :

testicle descent was barely earlier than in controls, testicle and prostate

weight were not increased, but seminal vesicle weight increased up to 40oJ6 . The tibia test showed an enlarged cleft: up to 1. 5 units (1 U = 25

in females, and up to 4 units in males.

N)

This apparently paradoxical result

will be discussed. The estimation of 17-KS excretion did not yield any significant results, as could be expected from the lack of weight change in the adrenals .

2) Rearing at 38~C At nearly fatal temperatures, 36 ± 1~ with 25% RH, mortality during

the 21 days of observation reached up to 50% .

The remaining rate showed

extreme stress reactions evident from Tables 1 and 2, especially extreme reductions in weight gain. The adrenals increased in weight up to 20% in females but not in males, thymus weight as well as swollen follicles decreased by 44-45°Jo .

The tibia test showed considerable shrinking of the cleft width.

Obviously, this heat stress reaction affected the females more than the males. The other parameters showed the same trend of deviations as described above, though at much higher percentages. B.

Development at Paired Feeding In this set-up a comparison was carried out of two groups of maturing

Female rata .

The first group was reared in the heat room at 34°C and 30oJ6 RH

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1197

EFFECT OF HEAT STRE83

with food and water supply ad libitum. The second was reared at the control temperature of 23gC and 80qó RH with food supply reduced to the level of the first group - water being $applied ad libitum. The results are compiled in Table 3.

It shows that reduced food intake

(35qó less) is the reason for the underdevelopment of rate reared at 30gó RH .

34° -

Supply of equal food rations at 23°C and 34gC may even allow better

weight gain in the group reared at the higher temperature .

The same trend

appears with regard to sexual development: uterine weight, vaginal opening, swollen follicles, corpora lutes and tibia teat.

There is, however, a signifi-

cant decrease due to heat in the weights of liver and kidneys, a fact to be discussed. Discussion The results obtained by rearing rata under conditions of heat stress show that the optimal temperature for their development lies at 28-28~C with 40qó RH (and higher).

With increasing heat, typical endocrine changes develop,

such as depressed body wéight but higher figures in the tibia teat for females and even very hígh figures for male rats .

This discrepancy has recently

been described by Parkhie and Johneon2g .

In an earlier paper we have shown

that the tibia test is stimulated by STH, insulin, testosterone, thyroxine and aldosteronel3 .

We feel, therefore, that the main reason for the increased

tibia test is the compensatory release of STH, insulin and testosterone to repair the catabolic heat effect.

For STH this has been recently proved 28 .

Decreased body weight due to heat exposure has been repeatedly described 27-34 . since the first reports by Sundatroem in 193014' That this decrease is due to reduced food intake and not to dehydration is evident from our results with paired feeding.

The reduction in liver and kidney weight by extreme

heat runs apparently parallel to the decrease in body weight .

Its relation to

food intake and metabolism is obvious but deserves further study.

The decrease in thyroid weight is self-explanatory, since numerous

papers have described the sensitivity of the hyperthyroid individual to heat 15-18 . exposure The same holds for heat suppression of thyroid activity in all species of animals since ín extreme heat conditions oxidation is kept at

lowest levels . Reduction oP thyroid activity by heat has been similarly desl9-21 . cribed with regard to rata

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EFFECT OF HEAT 3TRE88

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The adrenal weight is not influenced by heat as long as this dose not reach the nearly fatal temperature of 38°C . At 36°C only the females showed a stress reaction which could not be discerned in male rata . 22-24. This seems to be well in line with observations in man The thymus is not affected by heat between 30-34°C . At the excessive heat of 38~C, however, the stress produced increased adrenal weight and correspondingly decreased thymus weight .

This is the routine finding

encountered by us l. The moat impressive finding in the present study was the acceleration of sexual maturity of the females under heat stress due to FSH and LH release. This finding is also reflected in the weII-known fact that menarche in hot climates occurs in girls at the age of 12-13 years, instead of the usual 13-14 years.

This effect is not so marked in boys, and results with the male

rat seminal vesicles suggest that LH, rather than FSH is released . The mechanism of this effect has been much discussed25 and its enzyme kinesis , is now being studied bY us . The above observation was reported in 1930 14 35-36 . but later reports diverged without adequate explanations being given Pennycuik34 has pointed out that it may be connected with higher food energy utilization at 34~C . The hypothalamic centers which regulate both temperature maintenance and heat disposal mechanisms are intimately connected by descending pathways with the centers of the tropin-releasing factors of the median eminence and thus are able to exert the variety of endocrine effects described above.

We,

therefore, feel that moat of the heat effects observed here are apparently mediated by the hypothalamus .

This working theory becomes of immense

practical value if the fact is considered that above 38~C and 25°Jo relative humidity rats cannot be bred and most of them die.

Thus it follows that the

hypothalamus must be instrumental not only in heat regulation and the above

endocrine effects, but also for survival or death under eztreme heat conditions . This has induced ua to study new methods for prevention of lethal heat stress

mediated by the hypothalamus on which we shall report elsewhere.

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EFFECT OF HEAT 8TRE88 Summary

Rats of both sexes were reared immediately after weaning from the 21st to the 42nd day of life under various conditions of heat, ranging between 23-38°C, and relative humidity of between 20-40qó RH .

At higher temperatures

the rats did not survive.

Between 32-34°C, weights of body, liver, kidney and

thyroid were depressed.

Up to 34°C, the adrenals were hardly affected, but

in females they were enlarged at a temperature of 38°C .

The tibia test showed

the opposite effect, being highly increased in male rate and less so in female rats .

This was apparently due to a compensatory anabolic reaction of STH,

insulin and testosterone . The female sex organs were significantly stimulated by heat both at unlimited food intake and with paired feeding : vaginal opening was observed up to 5 days earlier, with uterine and ovary weights increased. However, testicle weight and prostate weight and testicle descent, were not significantly changed, whereas seminal vesicle weight increased by 40qó obviously due to testosterone release .

The above results are explained on

the basis of hypothalamus and pituitary hormone interactions mediated by the median eminence which is closely associated with the descending pathways of heat regulation . This paper was aided by a generous grant from the U. S. Department of Health, Education and Welfare, Environmental Health Service, Bureau of Occupational Safety and Health, Agreement No, 08-005-3 . We gratefully acknowledge the guidance and inspiration of the project officer: Dr . Austin Henschel . References 1.

S. DIKSTEIN, Y. KAPLANSKI, Y. KOCH, D. LOCKER and F. G. SULMAN, Growth 31, 301 (1987) .

2.

F. G. SULMAN, Arch . Internat. Pharmacodyn. & Thérap . 115, 354 (1958) .

3.

F. G. SULMAN and J. E. STEINER, Arch. Internat . Pharmacodyn. & Thérap. 121, 85 (1959) .

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F. G. SULMAN, Arch . Internat. Pharmacodyn. &_Thérap . 125, 497(1980) .

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A. EVIATAR, A. DANON and F. G. SULMAN, Arch . Internat . Pharmacodyn. & Thér~. 133, 75 (1981) .

EFFECT OF HEAT 3TRE33

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Vol . 9, No. 20

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