Conversion of T4 to T3 and rT3 and their cytoplasmic binding: pH dependency

The fate of T4 in target organs is conversion to T3 which is mainly responsible for the nuclear action of thyroid hormones. To further investigate this converting step the increase of T3 and its analogue rT3 in rat liver microsomes was measured by specific radioimmunoassays after adding T4 to the incubation medium. Maximal increase of T3 occurred at pH 6.0 and of rT3 at pH 9.5 indicating that two different enzymic systems may be involved in the deiodination of the tyrosyl or the phenolic ring of T4. An increase in the binding capacity of cytosol proteins for T4, T3 and rT3 with rising pH demonstrates that there is also a pH dependency of the cytoplasmic binding of these iodothyronines. These reaction conditions should not only be considered in in vitro experiments, but may also be of importance in modifying the availability of T3 for its nuclear receptors.