FURTHER STUDIES ON DIFFERENCES IN THE UPTAKE OF 131-I-TRIIODOTHYRONINE IN THE BRAINS OF MALE AND FEMALE RATS.

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ABSTRACT A sex difference in the uptake of T3–131I by the brain has been previously noted in white rats such that higher uptakes were routinely observed in females. It was believed that such differences in T3–131I uptake might be related to the conjugation of T3–131I to glucuronic acid, to the clearance rate of T3–131I by the liver, to a difference in the iodinated derivatives entering the blood from the liver or to the breakdown of the T3-glucuronide complex within the intestine. Investigation of these components of the enterohepatic metabolism of triiodothyronine in male and female rats revealed that there were no real sex differences at this point. Studies on the effect of testosterone propionate (TP) given either to adult or to newborn females suggest a direct effect of TP on the degradation of T3–131I. Thus, the CNS uptake of T3–131I in TP-treated adult females was reduced and more like that observed in males and the point at which the degradation rate exceeded the uptake rate occurred sooner. The effect of TP in the newborn androgen sterilized females was manifest only in the red blood cell uptake of T3, which was decreased and therefore more like that seen in males than in untreated females. It thus appears that the lower uptake of T3–131I by the male CNS is due in part at least to a higher degradation rate which decreases the amount of labeled T3 available for concentration in the brain more quickly than in the female. The female, on the other hand, has a higher plasma and RBC T3–131I level, which is apparently related to the somewhat slower degradation rate of the injected labeled hormone. From previous experiments, one might anticipate that such an elevation in available T3–131I would be associated with a slight increase in T3 uptake by nervous tissue. This was substantially what was observed. Thus, the sex difference in T3–131I uptake by the CNS of the white rat appears to be somewhat related to the intrinsic degradation rate of the injected hormone by the tissues, particularly as influenced by androgens. Other factors involving the enterohepatic circulation and metabolism of T3 may be involved, but only perhaps as influenced along with other tissues by androgens. Certainly no evidence for any sex difference in this very important area of thyroid hormone metabolism was observed under any of the experimental conditions studied here.