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Anti-Thyroidal Influence of Diiodotyrosine1
440
T. M. HUSTON AND K. N. MAY
bott Laboratories, North Chicago, Illinois. Tissue residuals were determined by the same firm. REFERENCES Cragg, B. G., D. H. L. Evans and L. H. Hamlyn, 1954. The optic ticteim of G. domesticus. J. Anat. (London) 88: 292-307.
Gandal, C. P., 1956. Satisfactory general anesthesia in birds. J. Amer. Vet. Met. Med. Assoc. 128: 332-334. Lee, C. C , 1953. Experimental studies on the actions of several anaesthetics in domestic fowls. Poultry Sci. 32:624-627. Warren, D. C , and H. M. Scott, 1935. The time factor in egg formation. Poultry Sci. 14: 195207.
Anti-Thyroidal Influence of Diiodotyrosine 1
(Received for publication May 30.1960)
I
T HAS been shown that the feeding of synthetic thyro-protein to hens increases the time required to hatch their eggs and results in the presence of goiters in chicks hatched from these eggs (Wheeler and Hoffmann, 1948a,b). The chicks are hypothyroid as shown by their lowered oxygen consumption rate (McCartney and Shaffner, 1949). These results are contradictory to those obtained when thyroprotein is fed directly to adult or growing chickens. In these cases metabolic rate is elevated and thyroid involution occurs (Wheeler, Hoffmann and Graham, 1948). Injection of thyroprotein into fertile eggs also results in thyroid involution in the developing chick (Booker and Sturkie, 1949). An explanation for these paradoxical effects became evident when Wolff and Chaikoff (1948a,b) reported that administration of large amounts of inorganic iodide inhibited thyroxine synthesis in the thyroid gland of normal rats. Later, Wheeler and Hoffmann (1949a, b; 1950) 1 Journal Series Paper No. 126, College Experiment Station, University of Georgia, Athens, Georgia. 2 Director of Instruction, College of Agriculture.
reported that K I can act as a goitrogenic agent in chicks and hens. When large amounts of iodide were injected into fertile eggs on the 16th day of incubation, the chicks exhibited marked thyroid enlargement at hatching. Moreover, these goitrous chicks exhibited typical hypothyroid symptoms: delayed hatching and delayed closure of the umbilicus. Goiters also developed in mature hens fed large amounts of inorganic iodide, and in chicks hatched from their eggs. Because of the similarity of effects on the thyroid of thyroprotein and KI, it was assumed that the high iodide content of thyroprotein might be responsible for its goitrogenic influence. However, when "iodide-free" thyroprotein was fed to hens, their chicks still exhibited the typical goiter (Wheeler and Hoffmann, 1950). It is possible, however, that sufficient amounts of iodide may be liberated in the metabolism of another component of thyroprotein, diiodotyrosine, to produce goiters. Thus, this current report concerns the influence of diiodotyrosine, when fed directly to chicks, or when incorporated in the diet of the dam, on chick thyroid weight.
Downloaded from http://ps.oxfordjournals.org/ at Kainan University on April 27, 2015
TILL M. HUSTON AND ROBERT S. WHEELER 2 Poultry Division, University of Georgia, Athens
441
ANTI-THYROIDAL INFLUENCE OF DIIODOTYROSINE EXPERIMENTAL
Age at autopsy
Diet
(wks.) 4 4 4 4
Basal Basal+0.02% KI Basal+0.02% Diiodotyrosine Basal+0.02% Thyroprotein
Paired thyroid weight (mg.±S.E.) 11.1 1.08 19.9 1.34 22.5 1.41 8.0 0.33
Basal Basal+0.01% Basal+0.02% Basal+0.02% Basal+0.02%
Desiccated Thyroid KI Diiodotyrosine Thyroprotein
2 2 2 2 2
9.2 7.2 13.1 13.0 5.8
0.38 0.61 1.12 1.04 0.21
Basal Basal+0.01% Basal+0.02% Basal+0.02% Basal+0.02%
Desiccated Thyroid KI Diiodotyrosine Thyroprotein
5 5 5 5 5
12.4 9.0 18.7 18.9 8.9
1.01 0.63 1.28 1.32 0.72
1
Ten chicks per group, five males and five females.
genicity. Presumably the influence of diiodotyrosine is indirect, mediated through the metabolism and liberation of iodide. Further study is needed to test this hypothesis. It is interesting to note that thyroid weight was reduced in chicks from hens fed a diet containing 0.01% desiccated thyroid powder. This is interpreted as evidence that dietary thyroxine is incorporated in the hen's egg. This thyroxine within the fertile egg could inhibit release of TSH from the chick pituitary and thus lead to the thyroid involution observed in the chick at hatching. Similar involuTABLE 2.—Thyroid weights of day-old chicks from hens fed diiodotyrosine, thyroprotein, or desiccated thyroid1
Diet of dam
•
Paired thyroid weights2 Males
Basal Basal+0.01% Basal+0.04% Basal+0.02% Basal+0.02% Basal+0.04%
(mg.iS.E.) 9.8 0.61 Diiodotyrosine 13.1 1.01 Diiodotyrosine 13.1 1.23 Thyroprotein 13.3 1.61 Desiccated Thyroid 6.3 0.32 Desiccated Thyroid 7.7 0.54
Basal Basal+0.01% Basal+0.04% Basal+0.02% Basal+0.02% Basal+0.04%
Diiodotyrosine Diiodotyrosine Thyroprotein Desiccated Thyroid Desiccated Thyroid
8.8 11.4 12.5 9.6 5.7 7.4
0.41 0.97 1.01 0.89 0.21 0.32
Females (mg.4 S.E.) 9.8 0.67 14.6 1.13 18.1 1.42 15.5 1.34 6 . 8 0.28 7.9 0.59 8.2 0.36 11.4 1.08 15.0 1.04 12.9 0.93 6 . 1 0.44 8.6 0.61
1 Hens on experimental diets for two weeks before eggs were saved for hatching. * Ten chicks per group, five males, five females.
Downloaded from http://ps.oxfordjournals.org/ at Kainan University on April 27, 2015
To test this hypothesis, groups of 10 New Hampshire hens in their first year of production were fed a conventional diet supplemented with diiodotyrosine, desiccated thyroid, KI, or thyroprotein. They were mated to males from the same flock. Excessive levels were used purposely since no previous thyroidal or anti-thyroidal influence had been attributed to diidotyrosine. Desiccated thyroid was used because no reports were available concerning the effects of administering this substance to dams, on thyroids of their newly hatched chicks. The hens had been on the experimental ration from 3 to 4 weeks at the time eggs were saved for incubation. At hatching 5 male and 5 female chicks were selected from each group and sacrificed by decapitation. The paired thyroids were dissected and weighed to the nearest 0.1 mg. on a Roller Smith balance. Other chicks from hens fed conventional diets were placed on diets containing KI, diiodothyrosine, or thyroprotein, soon after hatching. At 2, 4 and 5 weeks of age, samples of chicks were sacrified and the paired thyroids weighed as described above. The results are presented in Tables 1 and 2. When fed directly to chicks at excessive levels, diiodotyrosine and K I exert a goitrogenic influence of roughly equal magnitude (Table 1). This suggests that iodide, freed in the metabolism of diiodotyrosine, inhibits endogenous thyroxine secretion, which in turn is responsible for the observed compensatory thyroid enlargement. Diiodotyrosine or thyroprotein in the diet of the dam induces approximately the same degree of thyroid enlargement in chicks from these hens (Table 2). These results add weight to the suggestion that it is the diiodotyrosine content of thyroprotein that is responsible for its goitro-
TABLE 1.—Thyroid weights of chicks raised from date of hatch on diets containing KI, diiodotyrosine, thyroprotein, or desiccated thyroid'-
442
T. M. HUSTON AND R. S. WHEELER
tion was reported by McCartney and Shaffner (1949) and Booker and Sturkie (1949) when either thyroprotein or crystalline thyroxine solutions were injected into fertile incubating eggs. It is not possible to explain the lesser effect on the chick thyroid of increasing the amount of desiccated thyroid in a dam's diet. SUMMARY
REFERENCES Booker, E. E., and P. D. Sturkie, 1949. The effect of thyroxine and iodinated casein on the development of the chick thyroid. Poultry Sci. 28: 147-148. McCartney, M. G., and C. S. Shaffner, 1949. Chick thyroid size and incubation period as influenced by thyroxine, thiourical and thyroprotein. Poultry Sci. 28: 223-228. Wheeler, R. S., and E. Hoffmann, 1948a. Goitrous chicks from thyroprotein-fed hens. Endocrinology, 42: 326-328. Wheeler, R. S., and E. Hoffmann, 1948b. The value of thyroprotein in starting, growing and laying rations. Poultry Sci. 27: 509-514. Wheeler, R. S., E. Hoffmann and C. L. Graham, 1948. The value of thyroprotein in starting, growing and laying rations. Poultry Sci. 27: 103111. Wheeler, R. S., and E. Hoffmann, 1949a. Goitrous chicks from iodine injected eggs. Endocrinology, 45: 208-209. Wheeler, R. S., and E. Hoffmann, 1949b. Goitrogenic action of iodide and the etiology of goiters in chicks from thyroprotein-fed hens. Proc. Soc. Exp. Biol. Med. 72: 250-254. Wheeler, R. S., and E. Hoffman, 1950. The etiology of goiter in chicks from thyroprotein-fed hens; negative role of inorganic iodine. Poultry Sci. 29: 306-307. Wolff, J., and I. L. Chaikoff, 1948a. Plasma inorganic iodide, a chemical regulator of normal thyroid function. Endocrinology, 42: 468-471. Wolff, J., and I. L. Chaikoff, 1948b. The inhibitory action of iodide upon organic binding of iodine by the normal thyroid gland. J. Biol. Chem. 172: 855-856.
Residues of Coccidiostats in Poultry Tissues WALTHER H.
OTT
Merck Institute for Therapeutic Research, Rahway, N. J. (Received for publication May 30, 1960)
P
ROBLEMS relating to residues of coccidiostats in edible tissues of poultry are the same as for residues of food additives in general in animals for human
food use. If there is no residue of the coccidiostat in the food which man consumes, then the use of the compound cannot be characterized as hazardous to man. Thus,
Downloaded from http://ps.oxfordjournals.org/ at Kainan University on April 27, 2015
The goitrogenic action of increased iodide intake in growing chicks following continous dietary treatment was confirmed and an almost identical goitrogenic influence was observed in chicks fed excessive levels of diiodotyrosine. When diiodotyrosine was incorporated in the diet of hens, chicks from eggs laid by these hens exhibited goiters at hatching. This goitrogenicity was typical of that observed in chicks from hens fed a diet containing thyroprotein. These results suggest that the goitrogenicity of thyroprotein may be attributable to one of its major components; diiodotyrosine. It is further postulated that iodide liberated in the metabolism of diiodotyrosine inhibits thyroxine production which in turn leads to compensatory enlargement of the thyroid gland. Such an explanation serves equally well to account for the thyroid enlargement following direct administration of diidotyrosine to chicks or the goiters in chicks from hens fed diets con-
taining thyroprotein or diiodotyrosine in large amounts.
T. M. HUSTON AND K. N. MAY
bott Laboratories, North Chicago, Illinois. Tissue residuals were determined by the same firm. REFERENCES Cragg, B. G., D. H. L. Evans and L. H. Hamlyn, 1954. The optic ticteim of G. domesticus. J. Anat. (London) 88: 292-307.
Gandal, C. P., 1956. Satisfactory general anesthesia in birds. J. Amer. Vet. Met. Med. Assoc. 128: 332-334. Lee, C. C , 1953. Experimental studies on the actions of several anaesthetics in domestic fowls. Poultry Sci. 32:624-627. Warren, D. C , and H. M. Scott, 1935. The time factor in egg formation. Poultry Sci. 14: 195207.
Anti-Thyroidal Influence of Diiodotyrosine 1
(Received for publication May 30.1960)
I
T HAS been shown that the feeding of synthetic thyro-protein to hens increases the time required to hatch their eggs and results in the presence of goiters in chicks hatched from these eggs (Wheeler and Hoffmann, 1948a,b). The chicks are hypothyroid as shown by their lowered oxygen consumption rate (McCartney and Shaffner, 1949). These results are contradictory to those obtained when thyroprotein is fed directly to adult or growing chickens. In these cases metabolic rate is elevated and thyroid involution occurs (Wheeler, Hoffmann and Graham, 1948). Injection of thyroprotein into fertile eggs also results in thyroid involution in the developing chick (Booker and Sturkie, 1949). An explanation for these paradoxical effects became evident when Wolff and Chaikoff (1948a,b) reported that administration of large amounts of inorganic iodide inhibited thyroxine synthesis in the thyroid gland of normal rats. Later, Wheeler and Hoffmann (1949a, b; 1950) 1 Journal Series Paper No. 126, College Experiment Station, University of Georgia, Athens, Georgia. 2 Director of Instruction, College of Agriculture.
reported that K I can act as a goitrogenic agent in chicks and hens. When large amounts of iodide were injected into fertile eggs on the 16th day of incubation, the chicks exhibited marked thyroid enlargement at hatching. Moreover, these goitrous chicks exhibited typical hypothyroid symptoms: delayed hatching and delayed closure of the umbilicus. Goiters also developed in mature hens fed large amounts of inorganic iodide, and in chicks hatched from their eggs. Because of the similarity of effects on the thyroid of thyroprotein and KI, it was assumed that the high iodide content of thyroprotein might be responsible for its goitrogenic influence. However, when "iodide-free" thyroprotein was fed to hens, their chicks still exhibited the typical goiter (Wheeler and Hoffmann, 1950). It is possible, however, that sufficient amounts of iodide may be liberated in the metabolism of another component of thyroprotein, diiodotyrosine, to produce goiters. Thus, this current report concerns the influence of diiodotyrosine, when fed directly to chicks, or when incorporated in the diet of the dam, on chick thyroid weight.
Downloaded from http://ps.oxfordjournals.org/ at Kainan University on April 27, 2015
TILL M. HUSTON AND ROBERT S. WHEELER 2 Poultry Division, University of Georgia, Athens
441
ANTI-THYROIDAL INFLUENCE OF DIIODOTYROSINE EXPERIMENTAL
Age at autopsy
Diet
(wks.) 4 4 4 4
Basal Basal+0.02% KI Basal+0.02% Diiodotyrosine Basal+0.02% Thyroprotein
Paired thyroid weight (mg.±S.E.) 11.1 1.08 19.9 1.34 22.5 1.41 8.0 0.33
Basal Basal+0.01% Basal+0.02% Basal+0.02% Basal+0.02%
Desiccated Thyroid KI Diiodotyrosine Thyroprotein
2 2 2 2 2
9.2 7.2 13.1 13.0 5.8
0.38 0.61 1.12 1.04 0.21
Basal Basal+0.01% Basal+0.02% Basal+0.02% Basal+0.02%
Desiccated Thyroid KI Diiodotyrosine Thyroprotein
5 5 5 5 5
12.4 9.0 18.7 18.9 8.9
1.01 0.63 1.28 1.32 0.72
1
Ten chicks per group, five males and five females.
genicity. Presumably the influence of diiodotyrosine is indirect, mediated through the metabolism and liberation of iodide. Further study is needed to test this hypothesis. It is interesting to note that thyroid weight was reduced in chicks from hens fed a diet containing 0.01% desiccated thyroid powder. This is interpreted as evidence that dietary thyroxine is incorporated in the hen's egg. This thyroxine within the fertile egg could inhibit release of TSH from the chick pituitary and thus lead to the thyroid involution observed in the chick at hatching. Similar involuTABLE 2.—Thyroid weights of day-old chicks from hens fed diiodotyrosine, thyroprotein, or desiccated thyroid1
Diet of dam
•
Paired thyroid weights2 Males
Basal Basal+0.01% Basal+0.04% Basal+0.02% Basal+0.02% Basal+0.04%
(mg.iS.E.) 9.8 0.61 Diiodotyrosine 13.1 1.01 Diiodotyrosine 13.1 1.23 Thyroprotein 13.3 1.61 Desiccated Thyroid 6.3 0.32 Desiccated Thyroid 7.7 0.54
Basal Basal+0.01% Basal+0.04% Basal+0.02% Basal+0.02% Basal+0.04%
Diiodotyrosine Diiodotyrosine Thyroprotein Desiccated Thyroid Desiccated Thyroid
8.8 11.4 12.5 9.6 5.7 7.4
0.41 0.97 1.01 0.89 0.21 0.32
Females (mg.4 S.E.) 9.8 0.67 14.6 1.13 18.1 1.42 15.5 1.34 6 . 8 0.28 7.9 0.59 8.2 0.36 11.4 1.08 15.0 1.04 12.9 0.93 6 . 1 0.44 8.6 0.61
1 Hens on experimental diets for two weeks before eggs were saved for hatching. * Ten chicks per group, five males, five females.
Downloaded from http://ps.oxfordjournals.org/ at Kainan University on April 27, 2015
To test this hypothesis, groups of 10 New Hampshire hens in their first year of production were fed a conventional diet supplemented with diiodotyrosine, desiccated thyroid, KI, or thyroprotein. They were mated to males from the same flock. Excessive levels were used purposely since no previous thyroidal or anti-thyroidal influence had been attributed to diidotyrosine. Desiccated thyroid was used because no reports were available concerning the effects of administering this substance to dams, on thyroids of their newly hatched chicks. The hens had been on the experimental ration from 3 to 4 weeks at the time eggs were saved for incubation. At hatching 5 male and 5 female chicks were selected from each group and sacrificed by decapitation. The paired thyroids were dissected and weighed to the nearest 0.1 mg. on a Roller Smith balance. Other chicks from hens fed conventional diets were placed on diets containing KI, diiodothyrosine, or thyroprotein, soon after hatching. At 2, 4 and 5 weeks of age, samples of chicks were sacrified and the paired thyroids weighed as described above. The results are presented in Tables 1 and 2. When fed directly to chicks at excessive levels, diiodotyrosine and K I exert a goitrogenic influence of roughly equal magnitude (Table 1). This suggests that iodide, freed in the metabolism of diiodotyrosine, inhibits endogenous thyroxine secretion, which in turn is responsible for the observed compensatory thyroid enlargement. Diiodotyrosine or thyroprotein in the diet of the dam induces approximately the same degree of thyroid enlargement in chicks from these hens (Table 2). These results add weight to the suggestion that it is the diiodotyrosine content of thyroprotein that is responsible for its goitro-
TABLE 1.—Thyroid weights of chicks raised from date of hatch on diets containing KI, diiodotyrosine, thyroprotein, or desiccated thyroid'-
442
T. M. HUSTON AND R. S. WHEELER
tion was reported by McCartney and Shaffner (1949) and Booker and Sturkie (1949) when either thyroprotein or crystalline thyroxine solutions were injected into fertile incubating eggs. It is not possible to explain the lesser effect on the chick thyroid of increasing the amount of desiccated thyroid in a dam's diet. SUMMARY
REFERENCES Booker, E. E., and P. D. Sturkie, 1949. The effect of thyroxine and iodinated casein on the development of the chick thyroid. Poultry Sci. 28: 147-148. McCartney, M. G., and C. S. Shaffner, 1949. Chick thyroid size and incubation period as influenced by thyroxine, thiourical and thyroprotein. Poultry Sci. 28: 223-228. Wheeler, R. S., and E. Hoffmann, 1948a. Goitrous chicks from thyroprotein-fed hens. Endocrinology, 42: 326-328. Wheeler, R. S., and E. Hoffmann, 1948b. The value of thyroprotein in starting, growing and laying rations. Poultry Sci. 27: 509-514. Wheeler, R. S., E. Hoffmann and C. L. Graham, 1948. The value of thyroprotein in starting, growing and laying rations. Poultry Sci. 27: 103111. Wheeler, R. S., and E. Hoffmann, 1949a. Goitrous chicks from iodine injected eggs. Endocrinology, 45: 208-209. Wheeler, R. S., and E. Hoffmann, 1949b. Goitrogenic action of iodide and the etiology of goiters in chicks from thyroprotein-fed hens. Proc. Soc. Exp. Biol. Med. 72: 250-254. Wheeler, R. S., and E. Hoffman, 1950. The etiology of goiter in chicks from thyroprotein-fed hens; negative role of inorganic iodine. Poultry Sci. 29: 306-307. Wolff, J., and I. L. Chaikoff, 1948a. Plasma inorganic iodide, a chemical regulator of normal thyroid function. Endocrinology, 42: 468-471. Wolff, J., and I. L. Chaikoff, 1948b. The inhibitory action of iodide upon organic binding of iodine by the normal thyroid gland. J. Biol. Chem. 172: 855-856.
Residues of Coccidiostats in Poultry Tissues WALTHER H.
OTT
Merck Institute for Therapeutic Research, Rahway, N. J. (Received for publication May 30, 1960)
P
ROBLEMS relating to residues of coccidiostats in edible tissues of poultry are the same as for residues of food additives in general in animals for human
food use. If there is no residue of the coccidiostat in the food which man consumes, then the use of the compound cannot be characterized as hazardous to man. Thus,
Downloaded from http://ps.oxfordjournals.org/ at Kainan University on April 27, 2015
The goitrogenic action of increased iodide intake in growing chicks following continous dietary treatment was confirmed and an almost identical goitrogenic influence was observed in chicks fed excessive levels of diiodotyrosine. When diiodotyrosine was incorporated in the diet of hens, chicks from eggs laid by these hens exhibited goiters at hatching. This goitrogenicity was typical of that observed in chicks from hens fed a diet containing thyroprotein. These results suggest that the goitrogenicity of thyroprotein may be attributable to one of its major components; diiodotyrosine. It is further postulated that iodide liberated in the metabolism of diiodotyrosine inhibits thyroxine production which in turn leads to compensatory enlargement of the thyroid gland. Such an explanation serves equally well to account for the thyroid enlargement following direct administration of diidotyrosine to chicks or the goiters in chicks from hens fed diets con-
taining thyroprotein or diiodotyrosine in large amounts.