Endocrine Abstracts

The importance of thyroid hormone (TH) transporters to central nervous system (CNS) development has been highlighted by reports of severe global neurological impairment associated with mutations in the potent TH transporter, MCT8. Even subclinical maternal hypothyroidism in early pregnancy has been associated with long-term neurodevelopmental delay in the offspring suggesting that TH is crucial for early fetal brain development. The cellular entry of TH requires the function of specific plasma membrane transporters.

Objective: To describe the ontogeny of different TH transporters in the human fetal CNS.

Methods: Biopsies of cerebral cortex from human fetuses between 7 and 20 weeks gestation (wks; n=65) were obtained at surgical terminations of pregnancy and compared with adult cerebral cortex (n=10) with ethical approval. The relative mRNA expressions of nine TH transporters were quantified by Taqman RT-PCR.

Results: Messenger RNA encoding OATP1C1, OATP1A2 and OATP3A1 variant 2 were significantly lower at 7–16 wks compared with adult, with reductions of 98%, 95% and 91% respectively. Messenger RNA encoding LAT2 was 92% lower at 17–20 wks compared with adult, whilst LAT1 and the obligate heterodimer of the LATs, 4F2hc, showed no significant changes. MCT8, MCT10, OATP4A1 and OATP3A1 variant 1 mRNA expressions were similar to adult.

Conclusions: A range of TH transporters are present in the fetal cerebral cortex from very early gestation. These include OATPs previously localised to the blood brain barrier (BBB) in adult, MCT8 localised in CNS neurons and the choroid plexus (CP), and the LATs expressed in glial cell lines. The concerted effects of these transporters may play differential roles in the physiological regulation of TH entry into the fetal CNS at tissue and cellular levels. Thus, they may play a part in ensuring that the appropriate amounts of TH for each stage of CNS development are present to facilitate TH action.