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The Effects of Cortisone on the White Leghorn Cockerel and Capon1,2
The Effects of Cortisone on the White Leghorn Cockerel and Capon1'2 W I L L I A M E.
DULIN
Zoology Department, Indiana University, Bloomington,
Indiana3
(Received for publication April 6, 1954)
INTRODUCTION
T
HE physiological activity of cortisone on the rat and other mammals has been investigated extensively and an excellent review was recently published by Ingle and Baker (1953). Comparative studies, however, on other forms are meager. The purpose of the experiments reported in this paper was to determine the effects of this hormone on the chick. The fact that this hormone produces a decrease in body weight and adrenal atrophy has been described by many investigators (Moore, 1953; Winter, Silber and Stoerk, 1950; Wells and Kendall, 1940; and Lewis et ah, 1950). Antopol (1950) and Migeon (1952), however, have observed that this adrenal hormone has an inhibitory effect on the reproductive system of the mouse and rat. An inhibitory effect has also been reported to occur in the chick by cortisone treatment (Kudiza and Champion, 1953). In contrast to the above results it has been observed by Maddock (1953) that there occurs an increased excretion of gonadotropins in the human treated with cortisone, therefore, suggesting a stimulation of the pituitary-gonad axis. This same type of result has also been reported by Leroy (1951), who found an increase in
testis size in the rat, hamster, and chick resulting from this treatment. MATERIALS AND
METHODS
Single Comb White Leghorn cockerels and capons were used throughout these experiments. All birds were wing banded and animals which were caponized were operated on the 19th day of age. The body weights, and comb factors (height in mm. times length in mm. divided by 2) were determined prior to the first injection and the animals were assigned to series so that the average comb factors and body weights were as uniform as possible. There were two injection procedures used in these experiments. In the first, represented by data in Tables 1, 2, and 3, cortisone4 was administered subcutaneously in 0.2 ml. of normal saline from the 20th to the 39th day and the animals were autopsied on the 40th day. In the second, TABLE 1.—The effect of cortisone injected for 20 days on the body weights of cockerels and capons
1
Contribution No. 503 from the Department of Zoology, Indiana University, Bloomington, Indiana. 2 From part of a thesis presented to the faculty of the graduate school of Indiana University in partial fulfillment of the requirements for the Doctor of Philosophy degree in Zoology. 3 Present address: Research Laboratories, The Upjohn Company, Kalamazoo, Michigan.
No.
Dosage
Initial body weight
Final body weight
Gain
12 14 13 12
0 100 gamma 500 gamma 1,000 gamma
Cockerels 171 gms. 174 gms. 174 gms. 175 gms.
406 gms. 410 gms. 399 gms. 394 gms.
235 gms. 236 gms. 225 gms. 219 gms.
12 13 14 14
0 100 gamma 500 gamma 1,000 gamma
Capons 133 gms. 129 gms. 130 gms. 128 gms.
364 gms. 326 gms. 312 gms. 305 gms.
231 gms. 197 gms.* 180 gms. t 172 gms.t
' = . 0 5 when tested by the " t ' :' test.
t "P"' = . 0 1 . 4
The Cortisone used in these experiments was kindly supplied by Doctor Elmer Alpert of Merck and Company, Rahway, New Jersey.
73
74
W. E. DULIN TABLE 2.—Effects
of cortisone injected for 20 days on comb growth, testis weig and pituitary weights and potencies
No.
Dosage in gamma
Comb weight, mg. %l
12 14 13 12
0 100 500 1,000
623 522 659 546
15 15 11 13
0 50 100 200
709 552 512 428*
12 13 14 14
0 100 500 1,000
124 138 129 156*
Pituitary weights, mg. %
Pituitary 3 potencies
Cockerels (Exp. 1) 229 43.6 203 38.0 227 34.1* 212 35.0*
1.21 1.25 1.23 1.32
10.68 9.97 10.11 10.03 6.51 4
Cockerels (Exp. 2) 225 42.0 184 38.1 180 34.0* 160* 29. Of
1.20 1.32 1.22 1.24
10.01 10.39 10.78 10.66 5.08"
1.82 1.90 1.88 1.89
14.27 15.17 15.08 13.44 7.04 4
Testis weight, mg. % '
C.F. gain2
Capons 49 62f 62 f 72f
— — —
* " P " 0.05 when tested by the "t" test. t"P"=0.01. 1 Mg. per 100 gm. body weight. 2 Comb factor gains per 100 gm. body weight gain. 3 Pituitary potencies are represented by the average testis weights of 12 assay animals, each of which received 4.0 mg. equivalent fresh pituitary obtained from animals injected with cortisone or saline for 20 days. 4 Testis weights of assay animals receiving only saline.
represented by data in Table 4, the animals were injected intraperitoneally with cortisone in 0.4 ml. saline or only saline one hour prior to the subcutaneous injection of 0.4 ml. of 1:1000 epinephrine hydrochloride. These birds were treated from the 20th to the 24th day and autopsied on the 25th day of age. The comb factors and body weights were determined at the time of autopsy so the gains could be calculated. The testes, comb, adrenal, and pituitary weights were also determined at the time the animals were sacrificed. The pituitaries were stored in acetone until they were assayed. They were assayed for their gonadotropin content using the one day-old chick as the test animal according to the method of Byerly and Burrows (1939) and Breneman (1945).
RESULTS AND DISCUSSION
Body Weights: The effect of cortisone on body growth has been demonstrated by many investigators. Winter, Silber and Stoerk (1950) reported that 3.0 mg. of this hormone per day in the rat produced a cessation of body growth. Wells and Kendall (1940) and Lewis et al. (1950) also have shown that 1.0 and 1.25 mg. per day of cortisone administered to the rat caused a depression of body weight gain. Recently Kudiza and Champion (1953) have reported that 1.0 mg. per pound per day caused a significant weight loss in the mature male fowl but no such effect was demonstrated for the female. The data in Table 1 show the results of the effects of cortisone on immature cockerels and capons. I t is apparent that the weight gain of the intact animals was not
EFFECTS OF CORTISONE
75
altered by the treatment. The differences treated with cortisone. The results rebetween these observations and those of ported here are, however, in contrast to Kudiza and Champion may be due to the those reported by Leroy (1951), who reage difference of the animals. The capons, ported a stimulation of the testis and however, show a reduction of body growth comb growth by this treatment. at all dosage levels. The difference in reIt is noteworthy that the comb factor sponse of the intact animals and capons to gains of all the capon series treated with this steroid may be due to the fact that cortisone were significantly larger than the endogenous androgens present in the that of the capon controls. It is also seen cockerels are antagonistic to the catabolic from these data that the comb weights action of the adrenal hormone. This were not affected as much as the comb antagonistic effect of androgens and factors. It is felt, however, that in these glucocorticoids has also been suggested by experiments, the comb factor gains are Gaunt et al. (1952). They report that more indicative of comb growth than the there was more weight gain in rats treated comb weights since the actual gain was with testosterone propionate plus corti- determined and not just the final value. sone than in animals treated with corti- These results on comb growth are intersone alone. preted to mean that cortisone or one of its Pituitary-Gonad Interrelations: The metabolites is slightly androgenic. chick is an excellent animal for studies The fact that cortisone treatment concerning the pituitary-gonad axis be- caused a depression of testis weights in cause the comb is sensitive to small the intact animals could be interpreted as amounts of androgen and it can be ob- being due to a decrease in gonadotropin served at chosen intervals without sacri- secretion by the anterior pituitary or to a ficing the animal. Information on pituitary direct action on the gonads to inhibit their weights and potencies also can be readily ability to respond to the pituitary horobtained. Accordingly, the effects of cor- mones. Information bearing on these postisone on the cockerel and capon were sibilities was obtained from the pituitary studied and the results are summarized in data. It was observed that the pituitary Table 2. weights were not altered by the treatExamination of these data show that ment. The pituitaries were also assayed the treatment produced a decrease in for their gonadotropin content and it was testis weights in the intact birds. It should found that the potency of the pituitaries be noted that the comb growth was not from the treated birds was just as great as significantly depressed in all series. Al- that of the controls (Table 2). These rethough these values were not significantly sults on pituitary weights and potencies different from the control values, it should favors the hypothesis that the inhibition be pointed out that in all treated groups, of the gonads in the intact animals was with the exception of the 500 gamma dos- due to a direct action of the cortisone on age, there was some inhibition of comb the testis. growth. This suggests that even though Pituitary-Adrenal Interrelations: The they were not statistically significant, the fact that cortisone treatment produces differences are probably real. These re- atrophy of the adrenals of the rat has been sults agree with those of Kudiza and observed by many investigators (Wells Champion (1953) who reported a de- and Kendall, 1940; Lewis et al., 1950; and pression of fertility in mature chicks Winter et al., 1950). It is generally agreed
76
W. E. DULIN
TABLE 3.'—Effects of cortisone injected for 20 days on the adrenal weights of cockerels and capons
Dosage in gamma
Adrenal weights, Mg. % body weight
12 14 13 12
Cockerels 0 100 500 1,000
14.96 18.30 14.50 15.00
12 13 14 14
Capons 0 100 500 1,000
18.22 18.64 17.06 20.85
TABLE 4.—Effects of cortisone pretreatment on epinephrine induced adrenal hypertrophy Number
Treatment
Body weight
Adrenal weight
12 14 13
Controls 0.4 ml. Epinephrine 0.4 ml. Epinephrine plus 0.5 mg. Cortisone 0.4 ml. Epinephrine plus 1.0 mg. Cortisone 0.4 ml. Epinephrine plus 3.0 mg. Cortisone
181 176 171
30.8 mg.
175
34.8 mg.
175
34.0 mg
14
that this atrophy is brought about by suppression of adrenocorticotropin secretion by the anterior pituitary (Sayers and Sayers, 1949; and Lewis et al., 1950). It is obvious from the data in Table 3 that dosages of cortisone up to 1,000 gamma per day for 20 days had no effect on adrenal weights of the cockerel or capon. This lack of effect of cortisone on the adrenal growth of the chick may be due to the failure of the treatment to inhibit the secretion of the trophic hormone by the anterior pituitary or that the chick adrenal exhibits some activity independent of pituitary stimulation. This latter hypothesis has been suggested by Miller and Riddle (1942) to occur in the pigeon. The ability of cortisone to inhibit ACTH secretion was therefore tested by another experimental procedure. In this experiment, animals were pretreated with several dosages of cortisone given intraperitoneally one hour prior to injection of 0.4 ml. of a 1:1,000 solution of epinephrine hydrochloride. This type of treatment was used as a stress since it has been shown that it results in adrenal enlargement in the chick (Jailer and Boas, 1950; and Dulin, 1952). It has also been demonstrated that this adrenal enlargement is due to ACTH release from the anterior pituitary (Dulin, 1952).
9
42.8 mg.f 34.0 mg.
f "P"=0.01 when tested by the "t" test when compared to the adrenal weights of all other series.
The data in Table 4 summarize the mean adrenal and body weights of animals which received no cortisone or epinephrine, those which received only epinephrine and birds which were injected with both hormones. It is obvious from these data that the expected adrenal enlargement occurred in the epinephrine treated animals whose average adrenal weights were 47.8 mg. as compared to 30.8 mg. for the controls. Comparison of the adrenal weights of all series of animals which received cortisone plus epinephrine with those given only epinephrine demonstrates that cortisone pretreatment results in the inhibition of the adrenal enlargement produced by this type of stress. It should also be noted that the adrenal weights of the pretreated animals are not significantly different from those of the controls. These results indicate that the release of ACTH by the anterior pituitary following epinephrine injection is prevented by cortisone. Since this steroid hormone did not produce adrenal atrophy in the earlier experiments but it does inhibit the release of ACTH during epinephrine treatment suggests that the adrenals of the chick possess some activity independent of pituitary stimulation. SUMMARY
The body weight gain of White Leghorn cockerels was not affected by 100, 500, or 1,000 gamma of cortisone but the weight
EFFECTS OF CORTISONE
gains of capons treated with these amounts of hormone were reduced and this reduction was greater as the dosage was increased. It was suggested that the difference of effect on body growth of cockerels and capons may have been due to the presence of the androgen in the intact animal which is antagonistic to the catabolic action of the cortisone. Graded dosages of cortisone resulted in inhibition of testis growth and probably secretion in the unoperated animals but caused an increase in comb growth of the capons. The hypothesis was advanced that the inhibition in the cockerels was due to a direct action of the cortisone on the gonads since neither the pituitary weights or gonadotropic potency were altered by the treatment. This adrenal hormone failed to produce any alteration in adrenal size at dosages up to 1,000 gamma per day for 20 days. It was demonstrated, however, that 500 gamma of cortisone can prevent adrenal enlargement resulting from epinephrine injection. It was suggested that the chick adrenal may exhibit some activity apart from pituitary stimulation. REFERENCES Antopol, W., 1950. Anatomic changes produced in mice treated with excessive doses of cortisone. Proc. Soc. Exper. Biol. Med. 73: 262-265. Breneman, W. R., 1945. The gonadotropic activity of the anterior pituitary of cockerels. Endocrinol. 36: 190-199. Byerly, T. C , and W. H. Burrows, 1938. Chick testis weight responses to gonadotropic hormone. Endocrinol. 22: 366-369. Dulin, W. E., 1952. Studies on adrenal cortical function in the White Leghorn chick. Ph.D. Thesis, Indiana University. Gaunt, R. C , C. Howell and N. Antonchak, 1952. The effect of other steroids on the response to
77
cortisone. Abstracts of the 34th Meeting of the Endocrine Society. Ingle, D. J., 1950. The biologic properties of cortisone. J. Clin. Endocrinol. 10: 1312-1354. Ingle, D. J., and B. L. Baker, 1953. Physiological and Therapeutic Effects of Corticotropin and Cortisone, Charles C Thomas, Publisher, Springfield, 111. Jailer, J. W., and N. F. Boas, 1950. The inability of epinephrine or adrenocorticotropic hormone to deplete the ascorbic acid content of the chick adrenal. Endocrinol. 46: 314-318. Kudzia, J. J., and L. R. Champion, 1953. Investigations concerning the effects of cortisone in the domestic fowl. Poultry Sci. 32: 476-480. Leroy, P., 1951. Effects de la cortisone sur de testicule des mammiferers. Compt. Acad. Sci. 233: 976-978. Lewis, R. A., E. Rosemberg and L. Wilkins, 1950. The effects of 17-hydroxy-ll-dehydrocorticosterone upon the adrenals of normal and of hypophysectomized rats maintained with adrenocorticotropin. Endocrinol. 47: 414-417. Maddock, W. O., and J. D. Chase, 1953. The effects of large doses of cortisone on testicular morphology and urinary gonadotropin, estrogen and 17ketosteroid excretion. J. Lab. Clinical Med. 41: 608-614. Migeon, C. J., 1952. Effect of cortisone on lipids of serum, liver and testes in intact and adrenalectomized rats. Proc. Soc. Exper. Biol. Med. 80: 571-574. Miller, R. A., and O. Riddle, 1942. Cytology of the adrenal cortex of normal pigeons and in experimentally induced atrophy and hypertrophy. Am. J. Anat. 71:311-341. Moore, C. R., 1952. Adrenal cortical secretions in relation to the reproduction system of rats. J. Clinical Endocrinol. Metab., 13: 330-368. Sayers, G., and M. A. Sayers, 1949. The pituitaryadrenal system. Annals New York Academy of Sciences, 30: 522-539. Wells, B. B., and E. D. Kendall, 1940. The influence of corticosterone and C17 hydroxydehydrocorticosterone (compound E) on somatic growth. Proc. Staff Meeting, Mayo Clinic, 15: 324-328. Winter, C. A., R. H. Wilber and H. C. Stoerk, 1950. Production of reversible hyperadrenocortinism in rats by prolonged administration of cortisone. Endocrinol. 47: 60-72.
MARCH 17-19. THE PACIFIC DAIRY AND POULTRY ASSOCIATION CONVENTION, SALT LAKE CITY, UTAH
DULIN
Zoology Department, Indiana University, Bloomington,
Indiana3
(Received for publication April 6, 1954)
INTRODUCTION
T
HE physiological activity of cortisone on the rat and other mammals has been investigated extensively and an excellent review was recently published by Ingle and Baker (1953). Comparative studies, however, on other forms are meager. The purpose of the experiments reported in this paper was to determine the effects of this hormone on the chick. The fact that this hormone produces a decrease in body weight and adrenal atrophy has been described by many investigators (Moore, 1953; Winter, Silber and Stoerk, 1950; Wells and Kendall, 1940; and Lewis et ah, 1950). Antopol (1950) and Migeon (1952), however, have observed that this adrenal hormone has an inhibitory effect on the reproductive system of the mouse and rat. An inhibitory effect has also been reported to occur in the chick by cortisone treatment (Kudiza and Champion, 1953). In contrast to the above results it has been observed by Maddock (1953) that there occurs an increased excretion of gonadotropins in the human treated with cortisone, therefore, suggesting a stimulation of the pituitary-gonad axis. This same type of result has also been reported by Leroy (1951), who found an increase in
testis size in the rat, hamster, and chick resulting from this treatment. MATERIALS AND
METHODS
Single Comb White Leghorn cockerels and capons were used throughout these experiments. All birds were wing banded and animals which were caponized were operated on the 19th day of age. The body weights, and comb factors (height in mm. times length in mm. divided by 2) were determined prior to the first injection and the animals were assigned to series so that the average comb factors and body weights were as uniform as possible. There were two injection procedures used in these experiments. In the first, represented by data in Tables 1, 2, and 3, cortisone4 was administered subcutaneously in 0.2 ml. of normal saline from the 20th to the 39th day and the animals were autopsied on the 40th day. In the second, TABLE 1.—The effect of cortisone injected for 20 days on the body weights of cockerels and capons
1
Contribution No. 503 from the Department of Zoology, Indiana University, Bloomington, Indiana. 2 From part of a thesis presented to the faculty of the graduate school of Indiana University in partial fulfillment of the requirements for the Doctor of Philosophy degree in Zoology. 3 Present address: Research Laboratories, The Upjohn Company, Kalamazoo, Michigan.
No.
Dosage
Initial body weight
Final body weight
Gain
12 14 13 12
0 100 gamma 500 gamma 1,000 gamma
Cockerels 171 gms. 174 gms. 174 gms. 175 gms.
406 gms. 410 gms. 399 gms. 394 gms.
235 gms. 236 gms. 225 gms. 219 gms.
12 13 14 14
0 100 gamma 500 gamma 1,000 gamma
Capons 133 gms. 129 gms. 130 gms. 128 gms.
364 gms. 326 gms. 312 gms. 305 gms.
231 gms. 197 gms.* 180 gms. t 172 gms.t
' = . 0 5 when tested by the " t ' :' test.
t "P"' = . 0 1 . 4
The Cortisone used in these experiments was kindly supplied by Doctor Elmer Alpert of Merck and Company, Rahway, New Jersey.
73
74
W. E. DULIN TABLE 2.—Effects
of cortisone injected for 20 days on comb growth, testis weig and pituitary weights and potencies
No.
Dosage in gamma
Comb weight, mg. %l
12 14 13 12
0 100 500 1,000
623 522 659 546
15 15 11 13
0 50 100 200
709 552 512 428*
12 13 14 14
0 100 500 1,000
124 138 129 156*
Pituitary weights, mg. %
Pituitary 3 potencies
Cockerels (Exp. 1) 229 43.6 203 38.0 227 34.1* 212 35.0*
1.21 1.25 1.23 1.32
10.68 9.97 10.11 10.03 6.51 4
Cockerels (Exp. 2) 225 42.0 184 38.1 180 34.0* 160* 29. Of
1.20 1.32 1.22 1.24
10.01 10.39 10.78 10.66 5.08"
1.82 1.90 1.88 1.89
14.27 15.17 15.08 13.44 7.04 4
Testis weight, mg. % '
C.F. gain2
Capons 49 62f 62 f 72f
— — —
* " P " 0.05 when tested by the "t" test. t"P"=0.01. 1 Mg. per 100 gm. body weight. 2 Comb factor gains per 100 gm. body weight gain. 3 Pituitary potencies are represented by the average testis weights of 12 assay animals, each of which received 4.0 mg. equivalent fresh pituitary obtained from animals injected with cortisone or saline for 20 days. 4 Testis weights of assay animals receiving only saline.
represented by data in Table 4, the animals were injected intraperitoneally with cortisone in 0.4 ml. saline or only saline one hour prior to the subcutaneous injection of 0.4 ml. of 1:1000 epinephrine hydrochloride. These birds were treated from the 20th to the 24th day and autopsied on the 25th day of age. The comb factors and body weights were determined at the time of autopsy so the gains could be calculated. The testes, comb, adrenal, and pituitary weights were also determined at the time the animals were sacrificed. The pituitaries were stored in acetone until they were assayed. They were assayed for their gonadotropin content using the one day-old chick as the test animal according to the method of Byerly and Burrows (1939) and Breneman (1945).
RESULTS AND DISCUSSION
Body Weights: The effect of cortisone on body growth has been demonstrated by many investigators. Winter, Silber and Stoerk (1950) reported that 3.0 mg. of this hormone per day in the rat produced a cessation of body growth. Wells and Kendall (1940) and Lewis et al. (1950) also have shown that 1.0 and 1.25 mg. per day of cortisone administered to the rat caused a depression of body weight gain. Recently Kudiza and Champion (1953) have reported that 1.0 mg. per pound per day caused a significant weight loss in the mature male fowl but no such effect was demonstrated for the female. The data in Table 1 show the results of the effects of cortisone on immature cockerels and capons. I t is apparent that the weight gain of the intact animals was not
EFFECTS OF CORTISONE
75
altered by the treatment. The differences treated with cortisone. The results rebetween these observations and those of ported here are, however, in contrast to Kudiza and Champion may be due to the those reported by Leroy (1951), who reage difference of the animals. The capons, ported a stimulation of the testis and however, show a reduction of body growth comb growth by this treatment. at all dosage levels. The difference in reIt is noteworthy that the comb factor sponse of the intact animals and capons to gains of all the capon series treated with this steroid may be due to the fact that cortisone were significantly larger than the endogenous androgens present in the that of the capon controls. It is also seen cockerels are antagonistic to the catabolic from these data that the comb weights action of the adrenal hormone. This were not affected as much as the comb antagonistic effect of androgens and factors. It is felt, however, that in these glucocorticoids has also been suggested by experiments, the comb factor gains are Gaunt et al. (1952). They report that more indicative of comb growth than the there was more weight gain in rats treated comb weights since the actual gain was with testosterone propionate plus corti- determined and not just the final value. sone than in animals treated with corti- These results on comb growth are intersone alone. preted to mean that cortisone or one of its Pituitary-Gonad Interrelations: The metabolites is slightly androgenic. chick is an excellent animal for studies The fact that cortisone treatment concerning the pituitary-gonad axis be- caused a depression of testis weights in cause the comb is sensitive to small the intact animals could be interpreted as amounts of androgen and it can be ob- being due to a decrease in gonadotropin served at chosen intervals without sacri- secretion by the anterior pituitary or to a ficing the animal. Information on pituitary direct action on the gonads to inhibit their weights and potencies also can be readily ability to respond to the pituitary horobtained. Accordingly, the effects of cor- mones. Information bearing on these postisone on the cockerel and capon were sibilities was obtained from the pituitary studied and the results are summarized in data. It was observed that the pituitary Table 2. weights were not altered by the treatExamination of these data show that ment. The pituitaries were also assayed the treatment produced a decrease in for their gonadotropin content and it was testis weights in the intact birds. It should found that the potency of the pituitaries be noted that the comb growth was not from the treated birds was just as great as significantly depressed in all series. Al- that of the controls (Table 2). These rethough these values were not significantly sults on pituitary weights and potencies different from the control values, it should favors the hypothesis that the inhibition be pointed out that in all treated groups, of the gonads in the intact animals was with the exception of the 500 gamma dos- due to a direct action of the cortisone on age, there was some inhibition of comb the testis. growth. This suggests that even though Pituitary-Adrenal Interrelations: The they were not statistically significant, the fact that cortisone treatment produces differences are probably real. These re- atrophy of the adrenals of the rat has been sults agree with those of Kudiza and observed by many investigators (Wells Champion (1953) who reported a de- and Kendall, 1940; Lewis et al., 1950; and pression of fertility in mature chicks Winter et al., 1950). It is generally agreed
76
W. E. DULIN
TABLE 3.'—Effects of cortisone injected for 20 days on the adrenal weights of cockerels and capons
Dosage in gamma
Adrenal weights, Mg. % body weight
12 14 13 12
Cockerels 0 100 500 1,000
14.96 18.30 14.50 15.00
12 13 14 14
Capons 0 100 500 1,000
18.22 18.64 17.06 20.85
TABLE 4.—Effects of cortisone pretreatment on epinephrine induced adrenal hypertrophy Number
Treatment
Body weight
Adrenal weight
12 14 13
Controls 0.4 ml. Epinephrine 0.4 ml. Epinephrine plus 0.5 mg. Cortisone 0.4 ml. Epinephrine plus 1.0 mg. Cortisone 0.4 ml. Epinephrine plus 3.0 mg. Cortisone
181 176 171
30.8 mg.
175
34.8 mg.
175
34.0 mg
14
that this atrophy is brought about by suppression of adrenocorticotropin secretion by the anterior pituitary (Sayers and Sayers, 1949; and Lewis et al., 1950). It is obvious from the data in Table 3 that dosages of cortisone up to 1,000 gamma per day for 20 days had no effect on adrenal weights of the cockerel or capon. This lack of effect of cortisone on the adrenal growth of the chick may be due to the failure of the treatment to inhibit the secretion of the trophic hormone by the anterior pituitary or that the chick adrenal exhibits some activity independent of pituitary stimulation. This latter hypothesis has been suggested by Miller and Riddle (1942) to occur in the pigeon. The ability of cortisone to inhibit ACTH secretion was therefore tested by another experimental procedure. In this experiment, animals were pretreated with several dosages of cortisone given intraperitoneally one hour prior to injection of 0.4 ml. of a 1:1,000 solution of epinephrine hydrochloride. This type of treatment was used as a stress since it has been shown that it results in adrenal enlargement in the chick (Jailer and Boas, 1950; and Dulin, 1952). It has also been demonstrated that this adrenal enlargement is due to ACTH release from the anterior pituitary (Dulin, 1952).
9
42.8 mg.f 34.0 mg.
f "P"=0.01 when tested by the "t" test when compared to the adrenal weights of all other series.
The data in Table 4 summarize the mean adrenal and body weights of animals which received no cortisone or epinephrine, those which received only epinephrine and birds which were injected with both hormones. It is obvious from these data that the expected adrenal enlargement occurred in the epinephrine treated animals whose average adrenal weights were 47.8 mg. as compared to 30.8 mg. for the controls. Comparison of the adrenal weights of all series of animals which received cortisone plus epinephrine with those given only epinephrine demonstrates that cortisone pretreatment results in the inhibition of the adrenal enlargement produced by this type of stress. It should also be noted that the adrenal weights of the pretreated animals are not significantly different from those of the controls. These results indicate that the release of ACTH by the anterior pituitary following epinephrine injection is prevented by cortisone. Since this steroid hormone did not produce adrenal atrophy in the earlier experiments but it does inhibit the release of ACTH during epinephrine treatment suggests that the adrenals of the chick possess some activity independent of pituitary stimulation. SUMMARY
The body weight gain of White Leghorn cockerels was not affected by 100, 500, or 1,000 gamma of cortisone but the weight
EFFECTS OF CORTISONE
gains of capons treated with these amounts of hormone were reduced and this reduction was greater as the dosage was increased. It was suggested that the difference of effect on body growth of cockerels and capons may have been due to the presence of the androgen in the intact animal which is antagonistic to the catabolic action of the cortisone. Graded dosages of cortisone resulted in inhibition of testis growth and probably secretion in the unoperated animals but caused an increase in comb growth of the capons. The hypothesis was advanced that the inhibition in the cockerels was due to a direct action of the cortisone on the gonads since neither the pituitary weights or gonadotropic potency were altered by the treatment. This adrenal hormone failed to produce any alteration in adrenal size at dosages up to 1,000 gamma per day for 20 days. It was demonstrated, however, that 500 gamma of cortisone can prevent adrenal enlargement resulting from epinephrine injection. It was suggested that the chick adrenal may exhibit some activity apart from pituitary stimulation. REFERENCES Antopol, W., 1950. Anatomic changes produced in mice treated with excessive doses of cortisone. Proc. Soc. Exper. Biol. Med. 73: 262-265. Breneman, W. R., 1945. The gonadotropic activity of the anterior pituitary of cockerels. Endocrinol. 36: 190-199. Byerly, T. C , and W. H. Burrows, 1938. Chick testis weight responses to gonadotropic hormone. Endocrinol. 22: 366-369. Dulin, W. E., 1952. Studies on adrenal cortical function in the White Leghorn chick. Ph.D. Thesis, Indiana University. Gaunt, R. C , C. Howell and N. Antonchak, 1952. The effect of other steroids on the response to
77
cortisone. Abstracts of the 34th Meeting of the Endocrine Society. Ingle, D. J., 1950. The biologic properties of cortisone. J. Clin. Endocrinol. 10: 1312-1354. Ingle, D. J., and B. L. Baker, 1953. Physiological and Therapeutic Effects of Corticotropin and Cortisone, Charles C Thomas, Publisher, Springfield, 111. Jailer, J. W., and N. F. Boas, 1950. The inability of epinephrine or adrenocorticotropic hormone to deplete the ascorbic acid content of the chick adrenal. Endocrinol. 46: 314-318. Kudzia, J. J., and L. R. Champion, 1953. Investigations concerning the effects of cortisone in the domestic fowl. Poultry Sci. 32: 476-480. Leroy, P., 1951. Effects de la cortisone sur de testicule des mammiferers. Compt. Acad. Sci. 233: 976-978. Lewis, R. A., E. Rosemberg and L. Wilkins, 1950. The effects of 17-hydroxy-ll-dehydrocorticosterone upon the adrenals of normal and of hypophysectomized rats maintained with adrenocorticotropin. Endocrinol. 47: 414-417. Maddock, W. O., and J. D. Chase, 1953. The effects of large doses of cortisone on testicular morphology and urinary gonadotropin, estrogen and 17ketosteroid excretion. J. Lab. Clinical Med. 41: 608-614. Migeon, C. J., 1952. Effect of cortisone on lipids of serum, liver and testes in intact and adrenalectomized rats. Proc. Soc. Exper. Biol. Med. 80: 571-574. Miller, R. A., and O. Riddle, 1942. Cytology of the adrenal cortex of normal pigeons and in experimentally induced atrophy and hypertrophy. Am. J. Anat. 71:311-341. Moore, C. R., 1952. Adrenal cortical secretions in relation to the reproduction system of rats. J. Clinical Endocrinol. Metab., 13: 330-368. Sayers, G., and M. A. Sayers, 1949. The pituitaryadrenal system. Annals New York Academy of Sciences, 30: 522-539. Wells, B. B., and E. D. Kendall, 1940. The influence of corticosterone and C17 hydroxydehydrocorticosterone (compound E) on somatic growth. Proc. Staff Meeting, Mayo Clinic, 15: 324-328. Winter, C. A., R. H. Wilber and H. C. Stoerk, 1950. Production of reversible hyperadrenocortinism in rats by prolonged administration of cortisone. Endocrinol. 47: 60-72.
MARCH 17-19. THE PACIFIC DAIRY AND POULTRY ASSOCIATION CONVENTION, SALT LAKE CITY, UTAH