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Thyroxine Secretion Rates of Two Strains of New Hampshire Chickens Selected for High and Low Response to Thiouracil1
Thyroxine Secretion Rates of Two Strains of New Hampshire Chickens Selected for High and Low Response to Thiouracil 1 B. N. PREMACHANDRA, G. W. PIPES AND C. W. TURNER 2 Department of Dairy Husbandry, University of Missouri, Columbia (Received for publication September 20, 1957)
Journal Series No. 1794. Approved by the Director. 2 Aided-in-part by a grant from the U. S. Atomic Energy Commission, Contract No. AT(11-1)-301.
Determination of the Thyroxine Secretion Rate.—The birds were fed a 20% protein
399
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"D ECENTLY, Pipes el al. (1958) de- mine if further selection on this basis -*• *• scribed a radioiodine technique for would produce greater differences in the the in vivo estimation of thyroxine secre- thyroxine secretion rate of the two strains, tion rate in individual fowls. Using this and finally, by suitable crosses, to detertechnique, the thyroxine secretion rates mine the mode of inheritance of thyroxine were determined in individuals of two secretion rate. strains of New Hampshire chickens seThe object of the present paper is to relected for several generations on the basis port upon the individual thyroxine secreof high and low response to the feeding of tion rates of birds of these two strains as thiouracil (herein designated as the high measured by the I131 technique. In conand low lines). Hatching eggs from the low nection with this study, a number of inand high lines which had undergone 3 dices of thyroid function have been generations of selection were kindly sup- studied to note their relation to thyroxine plied by Dr. C. S. Shaffner of the Poultry secretion rate. Husbandry Department, University of EXPERIMENTAL Maryland. The eggs were hatched by the Poultry Husbandry Department of the Before proceeding with the determinaUniversity of Missouri and raised in our tion of thyroxine secretion rates, it was laboratory. The method of producing considered desirable to confirm that the these two lines of fowls has been reported two separate lines showed distinct differby El-Ibiary and Shaffner (1950). Shaklee ences in the degree of response when and Shaffner (1952) confirmed that varia- thiouracil was fed. Ten males about one tion in response was influenced by hered- year of age in each line were fed 0.1% ity after two generations of selection. Sub- thiouracil in the feed for a period of two sequently, the same authors (1955), em- weeks during November. They were then ploying the goitrogenic technique de- sacrificed, the thyroids were dissected free scribed by Mixner el al. (1944), were not of other tissues and immediately weighed able to demonstrate differences in average on a precision balance to the nearest 0.2 thyroxine secretion rates in these lines mg. The mean weight of the thyroids per after three generations of selection. 100 grams body weight in the high line was almost twice that in the low line. It seemed of interest to perpetuate While there was some over-lap in thyroid these strains of birds in order to study inweight/100 gm. body weight, the two dividual thyroxine secretion rate, to detergroups show rather definite differences 1 (Table 1). Contribution from the Missouri Agr. Exp. Sta.
400
B. N. PREMACHANDRA, G. W. PIPES AND C. W. TURNER
TABLE 1.—Variation in thyroid gland weight of high and low lines when fed 0.1% thiouracil
Band No.
Body weight, gm.
Thyroid gland weight, mg.
Thyroid weight per 100 gm. body weight
High Thyroid Line 3,450 240.6 3,340 390.2 2,885 366.6 3,180 245.4 3,450 458.2 2,900 464.4 3,315 441.2 2,635 260.2 3,000 317.6 2,755 199.2 3,091 338.4
6.97 11.68 12.71 7.70 13.28 16.01 13.31 9.87 10.59 7.23 10.94
11 12 13 14 15 16 17 18 19 Average
Low Thyroid Line 2,499 105.8 2,920 204.8 2,060 200.0 2,390 129.2 3,030 201.4 2,550 155.2 2,523 141.8 2,900 313.6 2,465 152.2 2,593 178.2
4.24 7.01 9.71 5.41 6.65 6.07 5.62 10.81 6.17 6.85
poultry ration. No attempt was made to control the iodine content of the ration. The method of Pipes et al. (1958) was used in the determination of the thyroxine secretion rate. The first step involved the
Following maximum iodine uptake the rate of release of thyroidal I131 was determined by in vivo measurement of thyroidal radio-active iodine each 24 hours. It was observed that the thyroidal
TABLE 2.—Comparative thyroid function in two lines of New Hampshire chickens
No. of birds
Line
131
% I uptake
Observed rate of release of thyroidal J181
(V)
Theoretical Experimental Thyroxine rate of secretion rate of release of release of rate, thyroidal thyroidal Mg./100 gm. J131 J131 body weight (*«")t (W
High thyroid enlargement
Males Females
24 26
54.8 51.0
0.0007 0.0015
0.0022 0.0038
0.0035 0.0043
1.01 1.03
Low thyroid enlargement
Males Females
20 24
49.5 40.5
0.0013 0.0016
0.0027 0.0039
0.0067 0.0098
2.89 3.08
There was no significant difference between sexes in the high line on any of the indices of thyroid function. In the low line the % uptake of I 131 was significantly higher (p<.01) in the males but the rate of release under thiouracil (W) (p<.05) was significantly higher in the females. The rate of release under thiouracil (ki") and the thyroxine secretion rate were significantly higher in low line (p<.001) when the two lines were compared. * Rate of release of thyroidal I 131 when theoretical assumptions are made to account for the recycling of iodine from the metabolized hormone. f Rate of release of thyroidal I 131 when reutilization of iodine from the metabolized hormone is prevented with a goitrogen like thiouracil.
Downloaded from http://ps.oxfordjournals.org/ at Univ of Iowa-Law Library on April 19, 2015
1 2 3 4 5 6 7 8 9 10 Average
subcutaneous injection of 50 juc. of carrierfree Nal 131 into each bird. Conventional corrections were made for the decay of the isotope and the background readings. All the results are expressed as percentage of administered dose of I131. In most of the birds maximum uptake was observed within 24 hours, although in some birds it continued for 48 hours. After maximum uptake was observed, the emanating radiation was almost exclusively from the thyroid region. The average percentage uptake of I131 by both males and females of the high line and the males of the low line were similar (Table 2). The females of the low line showed about 10% lower I131 uptake. Since the percentage uptake of iodine by all the birds was satisfactory, it was considered unnecessary to feed an especially low iodine diet. This might be necessary if low iodine uptakes were observed since diets very high in iodine tend to reduce I131 uptake.
THYROXINE SECRETION RATES
Brownell (1951) developed a correction equation by which the calculated degree of recycling of iodine could be determined. The corrected release rates (ki) by this method have been determined. It will be noted that the average ki values thus calculated are considerably increased in comparison with the k/ values (Table 2). One cause of the apparent low release rates of thyroidal I131 as indicated by the ki values is the well established fact that the tissues of the body metabolize I131tagged thyroxine with the release of I131 from the thyroxine molecule. This free I131 in the blood acts similarly to the original I131 injected and is again picked up by the thyroid gland. The recycling or reutilization of I131 from metabolized thyroxine reduces the true picture of the rate of I131 release to the extent of the amount picked up. In the application of the method of determining the thyroxine secretion rate, the index of equilibrium between the endogenous thyroxine secretion and the exogenous injection of thyroxine depends upon the cessation of release of I131 or upon the break in the curve of the rate of
release of thyroidal I131. In many birds the rate of release of thyroidal I131 is very low (ki values) and the change due to exogenous thyroxine is poorly defined. By the feeding of thiouracil at a level of 0.1% of the ration, the recycling of I131 can be prevented to a large extent. The apparent rate of release of thyroidal I131 is considerably increased. Under these conditions, the plateauing of the curve may be observed more readily with resulting increased accuracy in observing the end-point in the determination of thyroxine secretion (Figure 1). It is not necessary that thiouracil completely block the recycling of all the iodine from metabolized thyroid hormone. It will be noted that in both lines and in both sexes the ki" (release rate when recycling is prevented with thiouracil) rate increases in comparison with the ki values. It had been hoped that the ki" values might be closely related to the thyroxine secretion. It will be noted (Table 2) that the relationship is increased somewhat. It is suggested that the reason why the true release rate of the thyroid hormone (h") does not measure accurately the total daily thyroxine secretion rate is due to differences in the size of the thyroid gland. Thus, two birds of the same body weight and with equal release rates (ki") might vary in thyroxine secretion rate due to one having a larger thyroid with a larger potential capacity of secretion and storage of hormone. It should be emphasized that ki" is a measure of rate of release, but not of total thyroxine secretion. Total daily thyroxine released from the thyroid gland depends upon the amount of hormone available (related to size of thyroid gland) and the rate of release. It may also be pointed out that the theoretical correction for reutilization (£4) does not hold good for fowls under the conditions of the experiment when thiouracil is
Downloaded from http://ps.oxfordjournals.org/ at Univ of Iowa-Law Library on April 19, 2015
radio-activity from day to day diminished at an exponential rate, i.e., when plotted on semi-log charts it showed a straight line relation. The average rate of release of thyroidal I131, the ki exponent in the terminology of Brownell (1951), of the males and females of the two lines are presented (Table 2). The rate of release of thyroidal I131 represented by this exponent is uncorrected for the recycling of I131. While the males in each line show lower release rates (ki) than the females, the difference in the release rates of the two lines was not significant. That the ki values are poor indicators of thyroid function is shown by their comparison with ki or ki" exponents or the estimated thyroxine secretion rates of the two lines.
401
402
B. N. PREMACHANDRA, G. W. PIPES AND C. W. TURNER
THIOURACIL
0.1% OF RATION
605040 30-
c/i20 O Q
< >-
I r- 4 (TX=A-THYROXINE
~t
1
2"
3"
4
5
&
i
8" S DAYS
10-U
r/ioog"".}
12 13
14
15
16 17
FIG. 1. The method of estimation of the thyroxine secretion rate of individual birds of the high and low lines is indicated. The rate of release of thyroidal I131 is shown when the recycling of iodine is prevented by thiouracil. In the two birds of the high line with similar release rates ( k O , one (7545) required only 0.5 ^g. thyroxine per 100 gm. body weight to prevent the further release of thyroidal iodine I131, whereas the second (7634) bird required 1.0 Mg- Repeated thyroxine injections may be made in the same trial due to the rapid metabolism of the thyroxine. The great disparity between the two lines in thyroxine secretion rate, as well as in the rate of release of thyroidal I 131 when the recycling is blocked, can be clearly seen.
administered as a blocking agent. The glaring disassociation between k± and ki" can be seen in Table 2. The individual daily thyroxine secretion rates of 24 males and 26 females of the high line were determined. It will be noted that their average secretion rates are almost identical (Table 2). The average thyroxine secretion rate of the high line was 1.02 jug./lOO gm. body weight per day. The average daily thyroxine secretion rate of the males of the low line was slightly lower than that of the females with an average of 2.98 /ig./100 gm. body weight for the entire group. Thus, the strain of birds which showed a marked response to thiouracil by thyroid enlarge-
ment (high line) are low secreters of thyroxine, whereas the birds which showed a lower degree of response to thiouracil secrete almost three times as much thyroxine per day per 100 grams body weight. The frequency distribution of thyroxine secretion rate in the entire group of birds shows variations from 0.5 jug./100 gm. body weight to 6.0 jug. (Figure 2). The range in secretion rate of the high line (low thyroxine) is more limited than that in the low line indicating selection on the basis of the high response to the goitrogen is more effective than is the low response. While there is some overlap of secretion rate in the two lines, the degree of separa-
Downloaded from http://ps.oxfordjournals.org/ at Univ of Iowa-Law Library on April 19, 2015
J? = 10
THYROXINE SECRETION RATES
403
FIG. 2. The frequency distribution of the thyroxine secretion rate of the high and low line birds is shown. It will be noted that the low line shows greater variation in the thyroxine secretion rate than the high line. The extent of double hatching indicates the extent of overlap. The mean thyroxine secretion rate of the low line was 2.97 + 1.43 (C.V. 48.1%), whereas in the high line it was 1.01+0.474 (C.V. 46.9%).
tion of the two lines based upon the selection technique is quite remarkable. It may be possible, by the use of the thyroxine secretion rate as an index of selection, to separate the two lines completely. DISCUSSION A number of indices of thyroid function have been suggested since I1S1 began to be employed. These have included the percentage uptake, the rate of release of thyroidal iodine, (uncorrected or corrected for recycling), and finally, the determination of the thyroxine secretion rate. On the basis of the present study, it is believed that the only satisfactory index of thyroid function when animals are to be compared is the thyroxine secretion rate. The percentage of I131 uptake can be greatly influenced by the amount of
dietary iodine and probably variation in thyroid size. The rate of release of thyroidal I131 without control of the recycling of iodine from the metabolism of thyroxine I131 introduces sources of variation. The rate of release of thyroidal I131 with recycling controlled by a goitrogen is a satisfactory qualitative index of thyroid function in individual animals. Thus, seasonal changes (temperature) in W values in individual animals represent a true change in rate of release and of thyroid function. The differences in ki" values thus observed, however, cannot be translated into quantitative differences in thyroxine secretion rate. The marked difference in the average daily thyroxine secretion rates in relation to body weight of the two lines of birds during three generations of selection is
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a s to ~ts 2JO ZS io is 4s> 4.5 sjo sis eio 6.5 THYROXINE SECRETION RATE tr/lOOf*. BODY WX
404
B. N . PEEMACHANDRA, G. W. P I P E S AND C. W.
An alternative suggestion is t h a t there may be two thyrotropic factors (Greer, 1952), one which stimulates growth (hyperplasia) of the thyroid gland, and a second factor which stimulates the secretion and discharge of thyroxine. I t would be necessary to show t h a t the pituitaries of the high line secrete chiefly the thyrotropin stimulating thyroid hyperplasia and little thyrotropin stimulating thyroxine secretion, whereas the low line secreted, predominately, the thyrotropin stimulating thyroxine secretion. SUMMARY Two lines of New Hampshire fowls, selected for three generations on the basis of their response to the feeding of thiouracil by variation in average thyroid weight, were studied, using various indices of thyroid function. The average percentage uptake of I131 b y the two lines of birds, after 24 to 48 hours, was similar. The average rate of release of thyroidal
I 131 of the two lines was similar although the males in each line showed lower release rates t h a n the females. When the recycling of I181 from the metabolism of thyroxine was prevented by feeding thiouracil, the apparent release rates of thyroidal I 131 were increased. However, when the thyroxine secretion rate was determined in the two lines of birds, it was observed t h a t the line showing a marked response to thiouracil (high line) secreted an average of 1.02 /ig./100 gm. body weight of L-thyroxine, whereas the low line secreted an average of 2.98 ^g./lOO gm. body weight per day. While there was some over-lap of thyroxine secretion rate in the two lines, the degree of separation is quite remarkable. Two possible theories as to the cause of the differences in thyroid function in the two lines are presented. REFERENCES Brownell, G. L., 1951. Analysis of techniques for the determination of thyroid function with radioactive iodine. J. Clin. Endocrinology, 11: 1095-1105. El-Ibiary, H. M., and C. S. Shaffner, 1950. A genetic response to induced goiter in chickens. J. Heredity, 41: 246-248. Greer, M. A., 1952. The role of the hypothalamus in the control of thyroid function. J. Clin. Endocrinology 12: 1259-1268. Mixner, J. P., E. P. Reineke and C. W. Turner, 1944. Effect of thiouracil and thiourea on the thyroid gland of the chick. Endocrinology, 34: 168-174. Pipes, G. W., B. N. Premachandra and C. W. Turner, 1958. Measurement of the thyroid hormone secretion rate of individual fowls. Poultry Sci. 37: 36-41. Shaklee, W. E., and C. S. Shaffner, 1952. High and low thyroidal response to the feeding of thiouracil to New Hampshire chickens. J. Heredity, 43: 238-242. Shaklee, W. E., and C. S. Shaffner, 1955. Some effects of selecting for high and low thyroidal response to thiouracil feeding in New Hampshire chickens. Poultry Sci. 34: 572-577.
A U G U S T 5-8. P O U L T R Y S C I E N C E ASSOCIATION, A N N U A L M E E T I N G , C O R N E L L U N I V E R S I T Y , I T H A C A , N . Y.
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quite remarkable. I t m a y indicate t h a t the inheritance of thyroxine secretion via the pituitary-thyroid axis is governed b y a limited number of genes. These two lines of birds will provide favorable material for the study of the mode of inheritance of thyroxine secretion rate in fowls. These lines of birds will also provide valuable information in regard to the influence of thyroxine secretion rate upon growth and egg production. I t is interesting to speculate upon the reason for the line showing little response to the goitrogen being the greater secreters of thyroxine. Such a relationship could be explained if it could be shown t h a t this line has a low secretion of thyrotropin, but with thyroid glands very sensitive to thyrotropin as related to thyroxine secretion.
TURNER
Journal Series No. 1794. Approved by the Director. 2 Aided-in-part by a grant from the U. S. Atomic Energy Commission, Contract No. AT(11-1)-301.
Determination of the Thyroxine Secretion Rate.—The birds were fed a 20% protein
399
Downloaded from http://ps.oxfordjournals.org/ at Univ of Iowa-Law Library on April 19, 2015
"D ECENTLY, Pipes el al. (1958) de- mine if further selection on this basis -*• *• scribed a radioiodine technique for would produce greater differences in the the in vivo estimation of thyroxine secre- thyroxine secretion rate of the two strains, tion rate in individual fowls. Using this and finally, by suitable crosses, to detertechnique, the thyroxine secretion rates mine the mode of inheritance of thyroxine were determined in individuals of two secretion rate. strains of New Hampshire chickens seThe object of the present paper is to relected for several generations on the basis port upon the individual thyroxine secreof high and low response to the feeding of tion rates of birds of these two strains as thiouracil (herein designated as the high measured by the I131 technique. In conand low lines). Hatching eggs from the low nection with this study, a number of inand high lines which had undergone 3 dices of thyroid function have been generations of selection were kindly sup- studied to note their relation to thyroxine plied by Dr. C. S. Shaffner of the Poultry secretion rate. Husbandry Department, University of EXPERIMENTAL Maryland. The eggs were hatched by the Poultry Husbandry Department of the Before proceeding with the determinaUniversity of Missouri and raised in our tion of thyroxine secretion rates, it was laboratory. The method of producing considered desirable to confirm that the these two lines of fowls has been reported two separate lines showed distinct differby El-Ibiary and Shaffner (1950). Shaklee ences in the degree of response when and Shaffner (1952) confirmed that varia- thiouracil was fed. Ten males about one tion in response was influenced by hered- year of age in each line were fed 0.1% ity after two generations of selection. Sub- thiouracil in the feed for a period of two sequently, the same authors (1955), em- weeks during November. They were then ploying the goitrogenic technique de- sacrificed, the thyroids were dissected free scribed by Mixner el al. (1944), were not of other tissues and immediately weighed able to demonstrate differences in average on a precision balance to the nearest 0.2 thyroxine secretion rates in these lines mg. The mean weight of the thyroids per after three generations of selection. 100 grams body weight in the high line was almost twice that in the low line. It seemed of interest to perpetuate While there was some over-lap in thyroid these strains of birds in order to study inweight/100 gm. body weight, the two dividual thyroxine secretion rate, to detergroups show rather definite differences 1 (Table 1). Contribution from the Missouri Agr. Exp. Sta.
400
B. N. PREMACHANDRA, G. W. PIPES AND C. W. TURNER
TABLE 1.—Variation in thyroid gland weight of high and low lines when fed 0.1% thiouracil
Band No.
Body weight, gm.
Thyroid gland weight, mg.
Thyroid weight per 100 gm. body weight
High Thyroid Line 3,450 240.6 3,340 390.2 2,885 366.6 3,180 245.4 3,450 458.2 2,900 464.4 3,315 441.2 2,635 260.2 3,000 317.6 2,755 199.2 3,091 338.4
6.97 11.68 12.71 7.70 13.28 16.01 13.31 9.87 10.59 7.23 10.94
11 12 13 14 15 16 17 18 19 Average
Low Thyroid Line 2,499 105.8 2,920 204.8 2,060 200.0 2,390 129.2 3,030 201.4 2,550 155.2 2,523 141.8 2,900 313.6 2,465 152.2 2,593 178.2
4.24 7.01 9.71 5.41 6.65 6.07 5.62 10.81 6.17 6.85
poultry ration. No attempt was made to control the iodine content of the ration. The method of Pipes et al. (1958) was used in the determination of the thyroxine secretion rate. The first step involved the
Following maximum iodine uptake the rate of release of thyroidal I131 was determined by in vivo measurement of thyroidal radio-active iodine each 24 hours. It was observed that the thyroidal
TABLE 2.—Comparative thyroid function in two lines of New Hampshire chickens
No. of birds
Line
131
% I uptake
Observed rate of release of thyroidal J181
(V)
Theoretical Experimental Thyroxine rate of secretion rate of release of release of rate, thyroidal thyroidal Mg./100 gm. J131 J131 body weight (*«")t (W
High thyroid enlargement
Males Females
24 26
54.8 51.0
0.0007 0.0015
0.0022 0.0038
0.0035 0.0043
1.01 1.03
Low thyroid enlargement
Males Females
20 24
49.5 40.5
0.0013 0.0016
0.0027 0.0039
0.0067 0.0098
2.89 3.08
There was no significant difference between sexes in the high line on any of the indices of thyroid function. In the low line the % uptake of I 131 was significantly higher (p<.01) in the males but the rate of release under thiouracil (W) (p<.05) was significantly higher in the females. The rate of release under thiouracil (ki") and the thyroxine secretion rate were significantly higher in low line (p<.001) when the two lines were compared. * Rate of release of thyroidal I 131 when theoretical assumptions are made to account for the recycling of iodine from the metabolized hormone. f Rate of release of thyroidal I 131 when reutilization of iodine from the metabolized hormone is prevented with a goitrogen like thiouracil.
Downloaded from http://ps.oxfordjournals.org/ at Univ of Iowa-Law Library on April 19, 2015
1 2 3 4 5 6 7 8 9 10 Average
subcutaneous injection of 50 juc. of carrierfree Nal 131 into each bird. Conventional corrections were made for the decay of the isotope and the background readings. All the results are expressed as percentage of administered dose of I131. In most of the birds maximum uptake was observed within 24 hours, although in some birds it continued for 48 hours. After maximum uptake was observed, the emanating radiation was almost exclusively from the thyroid region. The average percentage uptake of I131 by both males and females of the high line and the males of the low line were similar (Table 2). The females of the low line showed about 10% lower I131 uptake. Since the percentage uptake of iodine by all the birds was satisfactory, it was considered unnecessary to feed an especially low iodine diet. This might be necessary if low iodine uptakes were observed since diets very high in iodine tend to reduce I131 uptake.
THYROXINE SECRETION RATES
Brownell (1951) developed a correction equation by which the calculated degree of recycling of iodine could be determined. The corrected release rates (ki) by this method have been determined. It will be noted that the average ki values thus calculated are considerably increased in comparison with the k/ values (Table 2). One cause of the apparent low release rates of thyroidal I131 as indicated by the ki values is the well established fact that the tissues of the body metabolize I131tagged thyroxine with the release of I131 from the thyroxine molecule. This free I131 in the blood acts similarly to the original I131 injected and is again picked up by the thyroid gland. The recycling or reutilization of I131 from metabolized thyroxine reduces the true picture of the rate of I131 release to the extent of the amount picked up. In the application of the method of determining the thyroxine secretion rate, the index of equilibrium between the endogenous thyroxine secretion and the exogenous injection of thyroxine depends upon the cessation of release of I131 or upon the break in the curve of the rate of
release of thyroidal I131. In many birds the rate of release of thyroidal I131 is very low (ki values) and the change due to exogenous thyroxine is poorly defined. By the feeding of thiouracil at a level of 0.1% of the ration, the recycling of I131 can be prevented to a large extent. The apparent rate of release of thyroidal I131 is considerably increased. Under these conditions, the plateauing of the curve may be observed more readily with resulting increased accuracy in observing the end-point in the determination of thyroxine secretion (Figure 1). It is not necessary that thiouracil completely block the recycling of all the iodine from metabolized thyroid hormone. It will be noted that in both lines and in both sexes the ki" (release rate when recycling is prevented with thiouracil) rate increases in comparison with the ki values. It had been hoped that the ki" values might be closely related to the thyroxine secretion. It will be noted (Table 2) that the relationship is increased somewhat. It is suggested that the reason why the true release rate of the thyroid hormone (h") does not measure accurately the total daily thyroxine secretion rate is due to differences in the size of the thyroid gland. Thus, two birds of the same body weight and with equal release rates (ki") might vary in thyroxine secretion rate due to one having a larger thyroid with a larger potential capacity of secretion and storage of hormone. It should be emphasized that ki" is a measure of rate of release, but not of total thyroxine secretion. Total daily thyroxine released from the thyroid gland depends upon the amount of hormone available (related to size of thyroid gland) and the rate of release. It may also be pointed out that the theoretical correction for reutilization (£4) does not hold good for fowls under the conditions of the experiment when thiouracil is
Downloaded from http://ps.oxfordjournals.org/ at Univ of Iowa-Law Library on April 19, 2015
radio-activity from day to day diminished at an exponential rate, i.e., when plotted on semi-log charts it showed a straight line relation. The average rate of release of thyroidal I131, the ki exponent in the terminology of Brownell (1951), of the males and females of the two lines are presented (Table 2). The rate of release of thyroidal I131 represented by this exponent is uncorrected for the recycling of I131. While the males in each line show lower release rates (ki) than the females, the difference in the release rates of the two lines was not significant. That the ki values are poor indicators of thyroid function is shown by their comparison with ki or ki" exponents or the estimated thyroxine secretion rates of the two lines.
401
402
B. N. PREMACHANDRA, G. W. PIPES AND C. W. TURNER
THIOURACIL
0.1% OF RATION
605040 30-
c/i20 O Q
< >-
I r- 4 (TX=A-THYROXINE
~t
1
2"
3"
4
5
&
i
8" S DAYS
10-U
r/ioog"".}
12 13
14
15
16 17
FIG. 1. The method of estimation of the thyroxine secretion rate of individual birds of the high and low lines is indicated. The rate of release of thyroidal I131 is shown when the recycling of iodine is prevented by thiouracil. In the two birds of the high line with similar release rates ( k O , one (7545) required only 0.5 ^g. thyroxine per 100 gm. body weight to prevent the further release of thyroidal iodine I131, whereas the second (7634) bird required 1.0 Mg- Repeated thyroxine injections may be made in the same trial due to the rapid metabolism of the thyroxine. The great disparity between the two lines in thyroxine secretion rate, as well as in the rate of release of thyroidal I 131 when the recycling is blocked, can be clearly seen.
administered as a blocking agent. The glaring disassociation between k± and ki" can be seen in Table 2. The individual daily thyroxine secretion rates of 24 males and 26 females of the high line were determined. It will be noted that their average secretion rates are almost identical (Table 2). The average thyroxine secretion rate of the high line was 1.02 jug./lOO gm. body weight per day. The average daily thyroxine secretion rate of the males of the low line was slightly lower than that of the females with an average of 2.98 /ig./100 gm. body weight for the entire group. Thus, the strain of birds which showed a marked response to thiouracil by thyroid enlarge-
ment (high line) are low secreters of thyroxine, whereas the birds which showed a lower degree of response to thiouracil secrete almost three times as much thyroxine per day per 100 grams body weight. The frequency distribution of thyroxine secretion rate in the entire group of birds shows variations from 0.5 jug./100 gm. body weight to 6.0 jug. (Figure 2). The range in secretion rate of the high line (low thyroxine) is more limited than that in the low line indicating selection on the basis of the high response to the goitrogen is more effective than is the low response. While there is some overlap of secretion rate in the two lines, the degree of separa-
Downloaded from http://ps.oxfordjournals.org/ at Univ of Iowa-Law Library on April 19, 2015
J? = 10
THYROXINE SECRETION RATES
403
FIG. 2. The frequency distribution of the thyroxine secretion rate of the high and low line birds is shown. It will be noted that the low line shows greater variation in the thyroxine secretion rate than the high line. The extent of double hatching indicates the extent of overlap. The mean thyroxine secretion rate of the low line was 2.97 + 1.43 (C.V. 48.1%), whereas in the high line it was 1.01+0.474 (C.V. 46.9%).
tion of the two lines based upon the selection technique is quite remarkable. It may be possible, by the use of the thyroxine secretion rate as an index of selection, to separate the two lines completely. DISCUSSION A number of indices of thyroid function have been suggested since I1S1 began to be employed. These have included the percentage uptake, the rate of release of thyroidal iodine, (uncorrected or corrected for recycling), and finally, the determination of the thyroxine secretion rate. On the basis of the present study, it is believed that the only satisfactory index of thyroid function when animals are to be compared is the thyroxine secretion rate. The percentage of I131 uptake can be greatly influenced by the amount of
dietary iodine and probably variation in thyroid size. The rate of release of thyroidal I131 without control of the recycling of iodine from the metabolism of thyroxine I131 introduces sources of variation. The rate of release of thyroidal I131 with recycling controlled by a goitrogen is a satisfactory qualitative index of thyroid function in individual animals. Thus, seasonal changes (temperature) in W values in individual animals represent a true change in rate of release and of thyroid function. The differences in ki" values thus observed, however, cannot be translated into quantitative differences in thyroxine secretion rate. The marked difference in the average daily thyroxine secretion rates in relation to body weight of the two lines of birds during three generations of selection is
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a s to ~ts 2JO ZS io is 4s> 4.5 sjo sis eio 6.5 THYROXINE SECRETION RATE tr/lOOf*. BODY WX
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B. N . PEEMACHANDRA, G. W. P I P E S AND C. W.
An alternative suggestion is t h a t there may be two thyrotropic factors (Greer, 1952), one which stimulates growth (hyperplasia) of the thyroid gland, and a second factor which stimulates the secretion and discharge of thyroxine. I t would be necessary to show t h a t the pituitaries of the high line secrete chiefly the thyrotropin stimulating thyroid hyperplasia and little thyrotropin stimulating thyroxine secretion, whereas the low line secreted, predominately, the thyrotropin stimulating thyroxine secretion. SUMMARY Two lines of New Hampshire fowls, selected for three generations on the basis of their response to the feeding of thiouracil by variation in average thyroid weight, were studied, using various indices of thyroid function. The average percentage uptake of I131 b y the two lines of birds, after 24 to 48 hours, was similar. The average rate of release of thyroidal
I 131 of the two lines was similar although the males in each line showed lower release rates t h a n the females. When the recycling of I181 from the metabolism of thyroxine was prevented by feeding thiouracil, the apparent release rates of thyroidal I 131 were increased. However, when the thyroxine secretion rate was determined in the two lines of birds, it was observed t h a t the line showing a marked response to thiouracil (high line) secreted an average of 1.02 /ig./100 gm. body weight of L-thyroxine, whereas the low line secreted an average of 2.98 ^g./lOO gm. body weight per day. While there was some over-lap of thyroxine secretion rate in the two lines, the degree of separation is quite remarkable. Two possible theories as to the cause of the differences in thyroid function in the two lines are presented. REFERENCES Brownell, G. L., 1951. Analysis of techniques for the determination of thyroid function with radioactive iodine. J. Clin. Endocrinology, 11: 1095-1105. El-Ibiary, H. M., and C. S. Shaffner, 1950. A genetic response to induced goiter in chickens. J. Heredity, 41: 246-248. Greer, M. A., 1952. The role of the hypothalamus in the control of thyroid function. J. Clin. Endocrinology 12: 1259-1268. Mixner, J. P., E. P. Reineke and C. W. Turner, 1944. Effect of thiouracil and thiourea on the thyroid gland of the chick. Endocrinology, 34: 168-174. Pipes, G. W., B. N. Premachandra and C. W. Turner, 1958. Measurement of the thyroid hormone secretion rate of individual fowls. Poultry Sci. 37: 36-41. Shaklee, W. E., and C. S. Shaffner, 1952. High and low thyroidal response to the feeding of thiouracil to New Hampshire chickens. J. Heredity, 43: 238-242. Shaklee, W. E., and C. S. Shaffner, 1955. Some effects of selecting for high and low thyroidal response to thiouracil feeding in New Hampshire chickens. Poultry Sci. 34: 572-577.
A U G U S T 5-8. P O U L T R Y S C I E N C E ASSOCIATION, A N N U A L M E E T I N G , C O R N E L L U N I V E R S I T Y , I T H A C A , N . Y.
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quite remarkable. I t m a y indicate t h a t the inheritance of thyroxine secretion via the pituitary-thyroid axis is governed b y a limited number of genes. These two lines of birds will provide favorable material for the study of the mode of inheritance of thyroxine secretion rate in fowls. These lines of birds will also provide valuable information in regard to the influence of thyroxine secretion rate upon growth and egg production. I t is interesting to speculate upon the reason for the line showing little response to the goitrogen being the greater secreters of thyroxine. Such a relationship could be explained if it could be shown t h a t this line has a low secretion of thyrotropin, but with thyroid glands very sensitive to thyrotropin as related to thyroxine secretion.
TURNER