The Metabolism of P-labeled Iodine, Thyroxine, and

Triiodothyronine in the Mammary Gland

of the Lactating Rat*

G. D. POTTER, WINTON TONG, AND I. L. CHAIKOFF

From the Department of Physiology, University of California, Berkeley, California

(Received for publication, October 8, 1958)

It has been known for many years that administered iodide appears in the milk of lactating animals. The early work on this subject was reviewed in 1937 by Elmer (1). Since that time, ample confirmation that the mammary gland secretes iodine has been obtained through experiments with radioactive iodide in man (Z-5) and a variety of animals (6-14). In rabbits (6, 8, 9) and goats (6), it has been shown that as much as half of an administered dose of I’s1 can be recovered in the milk produced. The mammary secretion of I’s1 proceeds so readily that thyroidal accumulation of administered 1’3l in lactating animals (8, 12, 13) has been found to be drastically reduced.

The iodine in milk, as studied by labeling with P31, has been reported to be mostly in the form of inorganic iodide in the case of man (3, 5), goats (6), rabbits (6, 8), and mice (13). In the dog, however, 30 to 60 per cent of the I1sl in milk was found in protein-bound form (7, 14). In a preliminary note (12), we showed that as much as 86 per cent of the I’s1 present in rat milk collected 24 hours after an Im-iodide injection was protein- bound. A value of 40 per cent was reported recently by Brown- Grant and Galton (15) for milk taken from rats 3 to 4 hours after I’s1 administration. Chromatographic analysis of an enzymatic hydrolysate of the milk revealed that the major P31-component in the protein was monoiodotyrosine. A small amount of P31- diiodotyrosine was also present, but no 1131-thyroxine was detected at various intervals up to 24 hours after the P31 injec- tions.

The present report deals with the following aspects of iodine metabolism in the rat mammary gland: (a) the transport of administered inorganic iodine into milk, and the form in which this iodine appears; (b) the effects of thyroidectomy and of thyroid inhibitors on the transport and organic binding of radioiodide by the mammary gland; and (c) the appearance of injected P31-thyroxine and P3’-triiodothyronine in milk.

EXPERIMENTAL

Treatment of A&r&s-The animals used were 17 to 19 day post-partum, lactating rats of the Long-Evans strain, reared on “Diablo Labration.” This diet contains about 2 pg. of iodine per gm. In order to deplete their mammary glands of stored milk, the lactating rats were kept with their litters until the start of each experiment. At that time, they were separated from their litters and were either given approximately 500 PC. of

* Aided by a grant from the United States Public Health Service.

P3i by intraperitoneal injection, or treated as indicated below. At intervals thereafter, the animals were anesthetized with Nembutal, and droplets of milk were expressed manually from the nipples and collected in centrifuge tubes with the aid of a small aspirator. Immediately thereafter, blood samples were withdrawn by cardiac puncture. Milk and blood samples were collected in tubes containing 20 ~1. of a 1 per cent solution of thiouracil which served to prevent organic binding of iodide during the subsequent treatment.

Milk samples were centrifuged at 3000 r.p.m. for 10 minutes and chilled in an ice bath to solidify the cream. The skim milk was withdrawn for analyses. Blood samples were similarly treated to separate plasma. As in the work of Honour et ~2. (3) and of Brown-Grant (8, 9), M :P (milk:plasma) ratios

total 1131 per ml. of milk

total P31 per ml. of plasma > were calculated to provide informa-

tion on the transfer of circulating plasma P3i into milk. Values for the total 1131 uptake by the mammary gland (in-

cluding its contained milk) were determined at the end of each experiment. The entire mass of mammary tissue was excised as completely as possible, and weighed. Then 4 to 8 representa- tive portions of approximately 100 mg. each were removed and homogenized in an all glass tissue grinder with 3 ml. of Krebs- Ringer bicarbonate buffer, and an aliquot of the resulting homog- enate was taken for 1’31 assay.

Chromatographic Analyses of Milk and Plasma-20 ~1. of skim milk and 40 ~1. of plasma were delivered directly onto filter paper strips for chromatography in collidine-water-ammonia (16). Another portion of skim milk (0.5 ml.) was incubated with 10 mg. of pancreatin for 24 hours, and 20 ~1. of the hy- drolysate were chromatographed as described above.

Radioautographs were prepared from the filter paper chroma- tograms, and those areas of the chromatograms corresponding to the darkened areas on the radioautograph were cut out and assayed for Ii3i.

P31 Determinations-These were carried out with a well type of scintillation detector (NaI . Tl).

1131-Labeled Thyroxine and Triiodothyronine-These com- pounds, obtained in 50 per cent propylene glycol solution from the Abbott Laboratories, were used for injections within 3 days after preparation. The labeled thyroxine (11 and 37 mc. of P3i per mg.) was found, by our chromatographic analyses, to contain 93 per cent thyroxine and 5 per cent inorganic iodide. The labeled triiodothyronine (37 mc. of P31 per mg.) showed 86 per cent triiodothyronine and 7 per cent iodide.

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February 1959 G. D. Potter, W. Tong, and I. L. Chaiko$ 351

RESULTS

Excretion of Injected Iodide into Milk-The results obtained with the first four rats (Table I) show that, at 24 hours after a single injection of carrier-free I 131, from 15 to 49 per cent of the injected radioactivity- was recovered in the mammary gland plus its contained and expressed milk. At all intervals, the concentrations of total 1131 in skim milk were many times higher than those in plasma (M : P ratios, Table I).

At 24 hours the 1131 present in the thyroid glands did not exceed 2 per cent in the lactating rats. In similar experiments with nonlactating rats the recovery of 113” in the thyroid glands was 6 to 8 per cent. This finding reflects the predominance, in utilization of circulating iodide, of the lactating mammary gland over the much smaller thyroid. Similar conclusions were reached by Rugh (13), with mice, and by Brown-Grant (8), with rabbits.

The addition of 100 pg. of carrier iodide to the injected 1131 did not significantly alter the extent of mammary utilization of the administered radioactivity, nor the M :P ratios attained (Table I).

Nature of 113’ in Rat JJilk-Results of chromatographic analyses of the skim milk obtained from I1sl-injected rats are shown in Table II. As reported earlier (12), a large part of the 1131 in the milk is bound to protein, and hence remains at the origin of the chromatograms. After treatment with pancreatic proteases, most of this protein-I131 was hydrolyzed, and the 1131 was recovered as 1131-monoiodotyrosine along with small amounts of 1’3’-diiodotyrosine. We failed to find the thyroxine-like components reported by Brown-Grant and Galton (15) on chromatograms of rat and rabbit milk hydrolysates; these com- ponents may have been iodotyrosine-containing peptides.

Iodide Transport in Mammary Tissue-Although values for the M : P ratio (column 7, Table I) suggest that the mammary gland actively secretes iodide into milk, certain limitations in \;he interpretation of such data should be considered. (a) ITnless the concentrations of organically bound 1131 in plasma and milk are negligibly low, this M : P ratio does not accurately reflect iodide-concentration gradients as does the T:S ratio

TABLE I Utilization o.f intraperitoneally injected Ils1 by mammary and

thyroid glands of lactating rats

Rat NO.

1’3’ injected

1 Carrier-free

2 Carrier-free

3 Carrier-free

4 Carrier-free

5 +100 /.Jg. 1’27

6 + 100 /.Jg. 1’2’

7 + 100 /Lg. 112’

Injected 1’3’ recovered in

oy$;nof thyroid

t 24 hours* a j

Hours fter in ection

M:P ratio Total

nammary issue plur

milk

%

25

21

49

15

14

34

17

Skim mi,k Plasma

% % Lwr nzl. per ml

1.04 0.031 1.10 0.095

1.50 0.042 1.06 0.060 0.0640.014 0.77 0.141 0.50 0.014 1.33 0.089

0.71 0.021 0.36 0.034 0.14 0.003:

0.40 0.022 0.23 0.008

%Y k! 1.5

1.3

1.1

2.1

1.0

0.6

0.8

1

24 6

24 6

24 3

24 6

24 6

24 6

24

34 12 36 18

46 5.5

36 15 34 11

38

I

* Thyroid glands weighed 14 to 18 my

TABLE II Distribution of I Is1 in skim milk obtained from lactating rats 24

hours after intraperitoneal injections of I1al

Per cent of 1’31 on chromatogram of

Unhydrolyzed skim milk Hydrolyzed skim milk Rat

NO. 1’3’ injected

8 Carrier-free 9 Carrier-free

10 Carrier-free 11 Carrier-free 5 + 100 pg. 1’27 6 +100 /Lg. 1’27 7 +100 pg. 1’27

Origin Diiodo- tyrosine

vlonoiodo- In- tyrosine rganic

10.1 5.0 52.8 31.2 6.2 6.4 46.5 41.3 6.0 6.4 46.5 41.3 7.3 6.7 68.0 17.9 9.8 5.5 54.5 30.2 6.8 8.3 64.5 20.5 8.8 7.3 65.5 17.8

-

( Kgin c

69 31 65 35 69 31 86 14

82 18 86 14

thyroid Il%odide cont.

serum I1%odide cont. used in thyroidal iodide trap studies.

(‘b) Because the iodide ;n milk stored in the mammary gland may not be in direct equilibrium with plasma iodide, it is pos- sible that the milk 1131 levels observed 6 hours or more after 1131 injection reflect largely the higher plasma iodide lcvcls prevailing during the earlier intervals after the injection. The experiments tlescribed in this section were designed to overcome these limita- tions and to reveal further the mechanism of iodide secretion in milk.

In order to establish values for the ratio of milk iodide-P31 to plasma iodide-P31 it was necessary either to block organic binding of 1131 by administration of propylthiouracil or to deter- mine iodide-113’ concentrations in milk and plasma by chromato- graphic analysis. In Table III, chromatographically determined milk iodide Ilsl to plasma iodide 1131 ratios are shown for three normal lactating rats (9-11). The values for this ratio, deter- mined at 6 hours after the 1131 Injection, were definitely lower than the corresponding values for the M:P ratio; nevertheless, they show that the iodide-I131 concentrations in milk were 6 or 7 times higher than those of blood plasma. Rats 14 to 16 (Table I I I) were treated with propylthiouracil, which blocked formation of protein-bound I 131 in milk (column 4) and in the thyroid gland (column 7). In these animals, the milk iodide Tls1 to

plasma iodide 1131 ratios attained higher values and, because of the depression of the protein-bound 1131 levels in the milk, became equal to the corresponding values for the M :P ratio.

In another experiment (Fig. I), lactating rats were first given, by intraperitoneal injection, 50 mg. of propylthiouracil and 30 minutes later, carrier-free 1131-iodide. Peak plasma 1’31 levels were established by assaying blood samples taken from the tail vein at 10, 15, 20, and 25 minutes after the injection of I1s1. Then, at 3 hours after the 1131 injection, milk and plasma samples were taken and assayed for I”‘. As shown in Fig. 1, the 1131 concentration in the skim milk was 10 times greater than the highest concentration of 1 131 found in the plasma during this interval. These results indicate that, even if the 113’ of stored milk is not in instantaneous equilibrium with the plasma 1131, the 1131 in the milk produced immediately after the 1131 injection must have been secreted against a plasma-to-milk iodide con- centration gradient.

Thiocyanate ion has been shown in studies in viva (17) and in vitro (18) to inhibit both iodide concentration and organic

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352 P-Iodide, Thyroxine, and Triiodothyronine in Mammary Gland Vol. 234, No. 2

TABLE III

Effects of thyroid inhibitors on utilization of 113* by mammary and thyroid glands o,f lactating rats

Rat Inhibitor NO injected

9 10 11 14

15

16

17 18 19 20 21 22

None None Xone Propylthi-

ouracil* Propylthi-

ouracil* Propylthi-

ouracil* KSCNt KSCNt KSCNt KClO,$ KClOd$ KC:lOJ

6 hours after 1’3’ injection -

M:P ratio

Protein bpi,fkI

o/o of tot on chron

togram

Milk W-iodide/

Plasma Pal-iodide

I -

1 rota1 mammarq tissue +

expressed and contained milk

rhyroid

12.6 42.0 7.3 11.2 44.0 6.3 16.7 60.7 6.6 21.8 2.5 21.3

% 24.3 19.6 45.6 31.3

-I

% 1.5 1.4 1.1 0.16

28.4 2.8 27.6 35.4 0.02

22.8 2.5 31.6 0.12

0.97 7.8 0.55 10.2 0.65 11.2 8.7 76.8 5.9 96.7 7.3 69.8

22.2

0.90 0 50 0.58 0.2 0.3 0.4

0.26 0.15 0.07 0.13 0.29 0.16 1.2 0.013 3.4 0.008 3.8 0.027

- 24 I hours after 1131 injection

njected 1131 recovered in

* 50 mg. of propylthiouracil injected intraperitoneally 30 min- utes before 1131-injection, and 25 mg. injected 4 hours after 1131- injection.

t 50 mg. of KSCN injected intraperitoneally 30 minutes before I’s’-injection, and 25 mg. injected 4 hours after 1131-injection.

$ 25 mg. of KC104 injected int,raperitoneally 30 minutes before 113L-inject,ion, and 12.5 mg. injected 4 hours after I’31-injection.

PLASMA 1 MILK fl

I I dl 0 30 60 I20 18C

MINUTES AFTER I”’

FIG. 1. Comparison of milk IIs1 concentration with peak plasma 1131 concentration in propylthiouracil-treated lactating rats. The 1’3’ concentrations shown here represent the average values for three rats.

binding in thyroid tissue. The results obtained with rats 17 to 19 (Table III) indicate that KSCN also inhibits organic binding (column 4), iodide concentration (column 5), and iodide uptake (column 6) by the mammary gland of the lactating rat.

Perchlorate ion is the most powerful inhibitor used in the study of the thyroidal iodide trap (19). As shown in Table III, it reduced the values for the milk iodide 1131 to plasma iodide 1’“’ ratio to values below 1 (column 5). Since it did not seem to

FIG. 2. Radioautographs of chromatograms of plasma and skim milk from a lactating rat 6 hours after an intraperitoneal injec- tion of 25 pg. (215 PC.) of 1131-l-thyroxine. Solvent, collidine- water-NH,j. 0, origin; Ta, thyroxine; I, inorganic iodide; SF, solvent front. The numbers on the right of each radioautograph show the percentages of the total 1’3’ present in each component of the chromatogram.

inhibit the formation of organic 1131 (column 4)) the corresponding M : P ratios still achieved values of 7.3 to 8.9.

Appearance of Injected P-Thyroxine and P-Triiodothyroninc in Milk-Our failure to detect labeled thyroxine in the milk or mammary tissue of 1131-injected lactating rats raised the question of whether thyroxine can be transported from the circulating plasma to milk. Therefore to eight lactating rats 1 to 25 pg. of l-thyroxine labeled with 34 to 213 PC. of 1131 were administered by intraperitoneal injection. Samples of milk and plasma obtained 6 and 24 hours later were esamined chromatographi- tally. Typical radioautographs prepared from these chromato- grams are shown in Fig. 2. Whereas 80 to 96 per cent of the 113’ in plasma was in the form of thyrosine, only 29 to 65 per cent of the milk-1131 was found in the thyroxine component. The remainder of the milk-1131 was present as inorganic iodide, re- leased presumably as a contaminant or decomposition product. of the thyrosine, along with varying amounts of iodoprotein formed from the inorganic iodide.

The concentrations of 1131-thyroxine in milk were one-tenth to one-quarter of those found in plasma (Table IV). The up- takes of the injected thyroxine-Ilzl by the mammary glands, determined at 24 hours after injection, ranged from 0.5 to 5 per cent of the injected dose. Iodide-P31 uptakes determined similarly were many times higher (cf. Tables I and III). Thus, it would appear that there is no mechanism for actively trans- porting thyroxine from plasma into milk as there is for iodide.

Similar experiments were carried out with I1”l-labeled triiodo- thyronine. As shown in Table V and Fig. 3, the proportion of injected triiodothyronine that appeared in the milk and mam- mary glands was quite comparable with that observed when I1al-thyroxine was injected. Unlike thyrosine, however, values calculated for the ratios of milk 1131-triiodothyronine to plasma 1131-tri’odothyronine were considerably above 1. Although these values do indicate that the concentration of triiodothyronine in milk can be greater than in plasma, it cannot be concluded that there is a mechanism for active secretion of triiodothyronine

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February 1959 G. D. Potter, W. Tong, and I. L. Chaikof 353

TABLE IV Recovery of injected P-thyroxine in skim milk of rats

6 hours after injection I 24 hours after injection

Per cent of injected 1’3’ recovered per ml. of Per cent of injected 1’31 recovered per ml. of

Rat No. Ta* injected

Milk Pla%Ki Milk T4

Plasma Ta Milk Ta

Plasma Tn

T4 Total T4 Total T4 Total T4

0.33 0.30 0.13 0.26 0.14 0.23 0.19 0.74 0.79 0.74 0.14 0.56 0.27 0.58 0.48 0.56

0.24 0.21 0.14 0.12 0.05 0.11 0.10 0.50 0.84 0.80 0.10 0.37 0.13 0.40 0.36 0.36

0.46 0.44 0.16 0.20 0.88 0.25 0.23 0.81 0.77 0.17 0.36 0.12 0.36 0.34

0.70 0.68 0.18 0.32 0.13 0.31 0.27 0.65 0.62 0.24 0.38 0.16 0.31 0.29

0.38 0.34

0.48 0.55

cl&,. 1

2

10

25

0.14 0.27

0.07 0.17

0.13 0.21

0.22 0.22

0.04 0.10

0.03 0.08

0.07 0.13

0.12 0.15 I

* 1’4 = thyroxine.

TABLE V Recovery of injected Z’31-tr%iodoth?lronine in skim milk o,f rats

6 hours after injection 24 hours after injection

Per cent of injected 1’3’ recovered per ml. of Per cent of injected 1131 recovered per ml. of Rat No. Ta* injected

1 2

3 4

5 6

-

_- - Milk Plasma Plasma

Milk TZ Plasma Ti

Total T3 Total T3 Total

0.28 0.09 0.06 0.15

0.07 0.02

0.02 0.05

0.03 0.11

0.012 0.003

7.5 5.0

0.09 0.22

0.07 0.43

0.02 0.12

0.003 6.7 0.021 5.7

0.03 0.23

0.013 2.5 0.064 3.6

0.20 0.14

0.21

0.53 0.18

Milk Ta

Plasma Ta

Total

0.0025 9.2 0.0018 2.8

0.02 0.0019 11.0

0.06 0.0086 5.2 0.03 0.0039 3.3

Milk

T3

0.023

0.005

0.020

0.045 0.013

* Ta = triiodothyronine.

into milk. It is possible that this finding is the result of the rapid disappearance rate of plasma triiodothyronine, and the fact that alveolar milk is not in direct equilibrium with the plasma.

UISCUSSION

The present and reported observations dealing with the elimination of administered 1131-iodide in the milk of lactating animals are tabulated in Table VI. It may be concluded from these tabulations that milk constitutes a major avenue for the elimination of iodine in the lactating animal. This diversion of circulating iodide into milk is reflected in a decreased re- covery of injected 1131 in the thyroid (8, 12, 13) and may explain in part the increased incidence of goiter in women during lact,ation

Gm . The utilization of iodide by mammary tissue may be divided

into two distinct processes: (a) active secretion of inorganic iodide into milk; and (b) a variable degree of incorporation of

this iodide into iodinated protein. The experiments described here dealing with the effects of propylthiouracil, thiocyanate, and perchlorate on the mammary utilization of 1131 show that it is the first of the two processes that determines the extent to which radioiodide is taken up by the mammary gland and secreted into milk. Thus, when only organic binding was blocked with propylthiouracil, the iodide secretion process was adequate to maintain high total uptakes by the mammary gland and to elevate the M:P ratios considerably. When only iodide secretion was blocked by KClOb, or when both iodide secretion and organic binding were blocked by KSCN, the M : P ratios and total uptakes were greatly reduced.

Our finding that 42 to 86 per cent of the P31 in the milk of radioiodide-injected rats is protein-bound differs somewhat from the observations reported on other animal species. For example, Rugh (13) reported that a small amount of the 1131 in mouse milk was protein-bound, although no mention is made of how this conclusion was reached. Brown-Grant (8) reported less than

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P-Iodide, Thyroxine, and Triiodothyronine in Mammary Gland Vol. 234, No. 2

FIN. 3. RadioautographS of chromatograms of plasma and skim milk from a lactating rat 6 hours after an intraperitoneal injection of 8 pg. (300 PC.) of 1’31-1-triiodothyronine. Solvent, butanol- ethanol-2 N NHIOH. 0, origin; I, inorganic iodide; T,, triiodo- thyronine; SF, solvent front. The numbers on the right of each radioautograph show the percent,ages of the total 1’31 present in each component of the chromatogram.

TABLE VI

Blzmination of administered I’al-iodide in milk or lactating animals

Animal

I :” Ammmtered 1131 recovered in milk and/or mammary gland

24 hours 48 hours ~-

% YO Mouse 65 to 78 31 to 89 Goat. 6 to 23 Rabbit. 21 to 49 Rat, 15 to 49

5 per cent trichloroacetic acid-precipitable Ilyl in rabbit milk, and Wright et al. (6) could detect no iodine compounds other than iodide in goat’s milk analyzed by paper chromatography. Finally, Miller and Weetch (5) found that the milk of a thyro- toxic woman contained less than 1.7 per cent zinc hydroside- precipitable 1131 at 10, 19, and 47 hours after In1 injection, and Honour et al. (3) found that all of the 1131 in the milk of two patients was dialyzable up to 19 hours after injection. Thus it seems that, of the sis species studied, the milk has been shown to contain iodinated protein only in the rat and the dog (7, 12).

Brown-Grant and Calton (15) were unable to detect thyrosine- 1131 in the milk of a rabbit up to 6 hours after an intravenous injection of labeled thyroxine. Hoskins et al. (21) concluded that, in their rats, maternal thyroxine was not secreted into milk in physiologically effective form since thyroxine adminis- tered to lactating rats together with propylthiouracil prevented goiter formation in the mother, but not in the suckling young. Our own findings with labeled thyroxine show that injected thyrosine does pass into the milk but not by any active secretory process and perhaps not in physiologically effective amounts.

SUMMARY

1. The mammary gland of the lactating rat is a major pathway for the elimination of iodine. As much as 50 per cent of circulat- ing iodide may be recovered in total mammary tissue plus milk in 24 hours.

2. At 6 hours after the injection of 1131, as much as 61 per cent, and at 24 hours as much as 86 per cent of the 1131 in rat milk was protein-bound. From 46 to 68 per cent of the 1131 in milk

Reference

was present as protein-bound monoiodotyrosine. A small amount of protein-bound, 1131-labeled diiodotyrosine was also found in rat milk. No other labeled compounds were detected.

3. The actions of propylthiouracil, thiocyanate, and per-

Rugh (13) chlorate on the iodide trap in the rat mammary gland and on the

Wright (6) organic binding of the 1131 in the milk expressed from 1131-injected

Brown-Grant (8) rats are discussed.

This report 4. Injected 1131-thyroxine and 1’31-triiodothyronine were shown to appear in the milk, but only in very small amounts.

1. ELMER, A. W., Iodine metabolism and thyroid junction, Oxford University Press, London, 1938.

2. NURNBERGER, C. E., AND LIECOMB, A., J. Am. Med. Assoc., 150, 1398 (1952).

3. HONOUR, A. S., MYANT, N. B., ANI) ROWLANDS, E. N., Clin. hi., 11, 447 (1952).

4. NOBLE, M. J. D., ANI) ROWLANES, S., J. Obstet. Gynaecol. Brit. Empire, 60, 892 (1953).

5. MILLER, H., AND WEETCH, R. S., Lancet, 269, 1013 (1955). 6. WRIGHT, W. E., CHRISTIAN, J. Ii;., AND ANI~REWS, F. N., J.

Dairy hi., 38, 131 (1955). 7. VAN MIUDLESWORTH, IA., TUTTLE, A. H., AND THRELKBLV, A.,

Science, 118, 749 (1953). 8. BROWN-GRANT, K., J. Physiol. London, 131, 70 (1956). 9. BROWN-GRANT, K., J. Physiol. London, 136, 644 (1957).

10. COURRIER, R., ROWE, J., DELTOUR, G. H., MAROIS, M., MICHEL. It.. AND MOREL. F., Compt. rend. sot. biol., 143, 599 (1949).

11. BUSTAD, L. K., GEORGE, L. A., MARKS, S., WARNER, D. E., BARNES, C. M., HERDE, K. E., AND KORNBERG, H. A., Radi- ation Research, 6, 380 (1957).

12. POTTER, G. D., AND CHAIKOFF, I. L., Biochim. et Biophys. Acta, 21, 400 (1956).

13. RUGH, R., J. Morphol., 89, 823 (1951). 14. VAN MIDDLESWORTH, L., TUTTLE, A. H., AND HANEY, D. F.,

Federation Proc., 13, 157 (1954).

15. BROWN-GRANT, K., AND GALTON, V. A., Biochim. et Biophys. Acta, 27, 422 (1958).

16. TAUROG, A., POTTER, G. D., CHAIKOFP, I. L., J. Biol. Chem., 213, 119 (1955).

17. VANDERLAAN, J. E., AND VANDERLAAN, W. I’., Endocrinology, 40, 403 (1947).

18. FRANKLIN, A. I,., CHAIKOFF, I. I,., AND WERNER, S. It., J. Biol. Chem., 163, 151 (1944).

19. WYNGAARDEN, J. B., WRIGHT, B. M., AND WAYS, P., Endo- crinology, 50, 537 (1952).

20. MARINE, D., in Glandular physiology and therapy, American Medical Association, Chicago, 1935, p. 345.

21. HOSKINS, L. C., VAN ARSDEL, P. P., AND WILLIAMS, R. H., Am. J. Physiol., 193, 509 (1958).

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G. D. Potter, Winton Tong and I. L. ChaikoffMammary Gland of the Lactating Rat

-labeled Iodine, Thyroxine, and Triiodothyronine in the131The Metabolism of I

1959, 234:350-354.J. Biol. Chem. 

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