Sex-Related Differences in Outer Ring Monodeiodination of Thyroxine and 3,3′,5′-Triiodothyronine by Rat Liver Homogenates*

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Abstract
The present studies were undertaken to evaluate possible sex-related differences in the peripheral outer ring deiodination of T4 to T3 in vitro by fresh liver homogenates. Hepatic T3 generation from T4 in female rats was similar to that observed in age-matched male rats from days 1-24. However, at 30 days of age, a significant decrease in T3 generation was observed in the female rat, becoming more pronounced with increasing age until puberty and then remaining approximately 50% of that observed in age-matched male rats through 90 days of age. In vitro addition of dithiothreitol, a thiol-protecting agent, did not affect these sex-related differences, suggesting a decrease in the 5′-deiodinating enzyme per se in the female rat rather than decreased concentrations of reducing cofactor(s). The sex-related differences in hepatic T4 to T3 conversion are related, at least in part, to sex steroids, since prepubertal castration at 20 days of age prevented these sex-related changes, and peripubertal castration at 40 days of age abolished these differences 46 days later. Testosterone administration enhanced hepatic T3 generation from T4 in the castrated male and female rats. /3-Estradiol administration decreased T3 generation in the orchiectomized male but enhanced or had no effect on in vitro T4 to T3 conversion in the ovariectomized female. In vitro degradation of [125I]rT3 was similar in the neonatal male and female rat but was decreased in the adult female compared to the adult male. Thus, the present studies strongly suggest that there are sex-related differences in outer ring deiodination of T4 to T.i and deiodination of rT3 by rat liver homogenates and that these differences are, at least in part, due to the sex steroids.