IODINE TRANSFER TO MILE ‘riod and again itravenous thy- shown that thiocyanate ion can act in the same ch experiment morning milk- mik-I"/plasma I™ ratio. blood I’ eon- ie I levels of manner. Concurrent with the decrease in milk radioiodine concentration was a decrease in the Two possibilities suggest themselves as explanations for these observations. One is that the chemicals given to the cows had an effect upon the iodide-concentrating mechanisin of the mammary gland. Another is that these chemicals induced the production of a new form of iodine not available for use in formation of milk. An earlier study comparing the blood and milk levels of radioiodine after a single dose produced results that hinted at the presence of forms of todine in blood which have different _availabilities for milk production (4). This was a possibility only for cows kept on lowiodine diets for a long time; for cows on high levels of dietary iodine there was no evidence that any form of iodine other than plasma iodide contributed detectable amounts of radioiodine for milk formation. Even for the cows on the low-iodine diet the deviation was not IXINE th a funetion of the mammary reater heights periment than was recelving nee thyroxine 2duee thyroid es during the of a lesser mmary gland ) restate that lese cows in ay the levels tes tended to on and any na were real ifferences in of samples. s paper that ‘an produce f radioiodine al. (3) have marked; therefore, a new form of iodine could be present only in small amounts. To produce changes of the magnitude observed in the experiments reported in this paper, marked changes in the composition of blood iodine would have to be present. Data on blood iodine fractionation for the KC1O, experiment of this paper and of a Nal experiment carried out previously (6) do not support this possibility. Using KCIO, (Figure 1), Nal (6), and NaSCN (3) the milk and blood levels of dairy cows were altered within 12 hr of administration of the chemical. Experiments by Brown- Grant using rabbits have shown that KSCN, KCIO,, and KI ean alter the m/p ratio within 1 hr (1). It is not likely that the appearance of a new form of labeled iodine could take place so rapidly. Another factor that minimizes the probability of a new form of iodine is that this new form must transfer with diffieulty across the cells of mammary gland and the thyroid, but must be able to be readily filtered by the kidney. It has been well aceepted that KI, KSCN, and KCIO, aet to interfere with the iodideconcentrating mechanism of the thyroid gland. Therefore, in addition to the qualifications de- tailed above, there is little reason to try to explain the action of these chemicals other than as an effect on the iodide-concentration mechanism of the mammary gland. Data of Table 1 show that the effeet of a substance such as KCI1O, is not adequately deseribed simply by indicating how much milk radioiodine was decreased. Blood levels of (5) radioiodine might inerease and so minimize the magnitude of the change. When milk I™ values are divided by plasma I™values to give a milk/ plasma ratio, an index is achieved which de- seribed the over-all ability of the mammary gland to concentrate iodine during production of milk. Sueh a device has been used in expressing results in this paper. To be more precise, however, the ratio should be the milk I'*/plasma-nonbound I" (4). If the proportion of plasma bound-I™is small, and does not change markedly as a stress is applied to the system, then the milk-I'"/plasma-I™is sufficient to it of in chart the magnitude of changes, even though underestimates, to some degree, the ability the gland to concentrate radioiodme. Data this and other publications have indicated that the milk/plasma Iratios in dairy cows ean vary from 0.3 to somewhat more than 35. This upper value, however, is markedly less than the 20 or 30 observed in other species (2). Changes in the milk/plasma ratios strongly suggest that the manner in which radioiodine concentration in milk was reduced was a direct action of the chemicals at the mammarygland. The depression of the iodide accumulation seems similar to that exhibited by the iodidetrap of the thyroid gland when acted upon by these substances. That the milk/plasma radio- iodine ratio was severely depressed by these chemicals suggests that the accumulation of iodide in milk is at least in part an active process. In the presence of the inorganic substances that inhibited iodide transfer the miulk/plasma ratio was observed to be as low as 0.3. The presence of this radioiodine in milk under these conditions implies that a passive transfer of iodide into milk also takes place. That the milk/plasma ratio ean be much less than one suggests that iodide does not readily diffuse across the membranes of the mammary gland during passive transfer. Milk/plasma ratios above 0.3, and certainly those above 1, may indicate that the active accumulation is operating to raise milk iodide levels up to or above that of the plasma. When the ratios are above 1, it can be assumed that the rate of transfer from plasma to milk exceeds that of the reverse movement. While it is evident that perchlorate, thiocyanate, and excess iodide can inhibit the active transfer from plasma to milk, it is not possible at this time to estimate their influence upon the reverse movement. Of interest was the demonstration that thyroxine eould bring about a reduction in the ability of the mammary gland to concentrate lodide in milk.