Sex-related differences in iodothyronine metabolism in the rat: Evidence for differential regulation among various tissues

Abstract

Various aspects of thyroid hormone metabolism were examined in vitro in age-matched (experiment I) and weight-matched (experiment II) male and female Sprague-Dawley rats; unless specified otherwise, results were similar in both experiments. The activity and content of iodothyronine 5′-monodeiodinase (type I-MD) in the liver of the female rat were markedly reduced, but there was no sex-related difference in these parameters in the kidney. The activity of the brain type III-MD was also not significantly influenced by the sex of the rat. Hepatic triiodothyronine (T 3) sulfation activity in the females was only about 20% of that of the males. However, kidney and brain did not show this decrease in T 3 sulfation. Similarly, hepatic T 3 sulfate (T 3S) desulfation activity was significantly reduced in the liver of the female rat ( P < .001), whereas the activity in the kidney was either similar to (experiment I) or higher than (experiment II) that in the male, and the activity in the brain was similar in the two sexes. The mean serum T 3S concentration in the female rat was no greater than 25% of the corresponding value measured in the male rat. The mean serum thyroxine (T 4) concentration in female rats was similar to that in age-matched males (experiment I), whereas it was somewhat lower than that in weight-matched males ( P < .05, experiment II). No significant difference in the mean serum T 3 concentration was observed in rats of female and male sex. However, the mean serum thyrotropin (TSH) concentration in the female rat was significantly lower than that in the male. The serum concentration of growth hormone (GH) was also significantly lower in the female than in the male in one experiment (II), but not in the other (I). Our data suggest that (1) the regulation of type I-MD is different among tissues; (2) T 3 sulfation activity and T 3S desulfation activity in various tissues involve different enzymes or different mechanisms of regulation; (3) hepatic T 3-sulfotransferase activity, which is predominant in the male, is the major source of circulating T 3S; (4) a complex balance of changes in T 3 generation and metabolism (T 3 sulfation, T 3S desulfation, and deiodination) is involved in the maintenance of normal serum T 3 and the euthyroid state in the female versus the male rat.