Figure 3. Strongly diminished uptake of T4 into the brain in the absence of MCT8 and OATP1C1.

(A) For in vivo transport studies, adult animals (n = 3 per genotype and time point) were injected i.p. with 1.2 μCi [¹²⁵I]T4. A blood sample was obtained, after which animals were perfused with PBS, and brains, livers, and kidneys were collected. The amount of radioactivity was expressed as percentage of the injected dose per gram of tissue. Whereas the amount of radioactivity in blood and liver samples did not differ among mutant groups, Mct8 KO and Mct8/Oatp1c1 DKO mice showed increased renal radioactivity at all analyzed time points. Most importantly, transport of radiolabeled T4 into the brain was strongly diminished in Mct8/Oatp1c1 DKO mice, whereas in the single-mutant animals, T4 uptake was reduced to approximately 50% of the respective WT levels. ^#P < 0.05, Mct8 KO vs. WT; ^§P < 0.05, Mct8/Oatp1c1 DKO vs. WT; ^‡P < 0.05, Oatp1c1 KO vs. WT. (B) Animals at P21 (n = 8 per genotype) were perfused with PBS before forebrains were collected for determining tissue TH concentrations. The concomitant inactivation of both TH transporters resulted in a pronounced decline of both T3 and T4 to approximately 10% of the levels in WT animals, which indicated that only Mct8/Oatp1c1 DKO mice exhibit a severe hypothyroid state in the CNS. ***P < 0.001 vs. WT, or as otherwise indicated (brackets).