Diverse effects of mild and potent goitrogens on blood-brain barrier nutrient transport

Populations living in goitre endemic areas consume foods rich in a variety of goitrogens of different potencies and some are severely hypothyroid. Recently we observed in Wistar/NIN rats that chronic feeding of KSCN to dams produced only a moderate hypothyroidism and decreased the transport of 2-deoxy-D-glucose (2-DG) across the blood-brain barrier (BBB) in the offspring. The present studies were conducted to assess whether severe hypothyroidism would have greater effect on BBB nutrient transport. It has now been observed that weaning the pups of KSCN fed dams on to KSCN diet for four weeks had no further effect either on their thyroid status or the BBB 2-DG transport. However, feeding KSCN to rats through two generations produced somewhat severe hypothyroidism in F2 pups than that in F1 pups. Interestingly, unlike in F1 pups, the BBB transport of all the three nutrients tested (2-DG, Leu and Tyr) was significantly decreased in F2 pups, albeit to a small extent (10-15%). On the other hand the potent goitrogen: methyl mercaptoimidazole (MMI) even on short term feeding to pregnant dams produced very severe hypothyroidism in the offspring [Serum T4:0.55+/-0.09 microg/dl vs 4.96+/-0.85 in controls]. Surprisingly, the BBB transport of 2-DG, Leu, Tyr and also sucrose, the background marker, was significantly increased in these pups (20-30%). The diverse effects of goitrogen-induced moderate and severe hypothyroidism observed here on the BBB nutrient transport probably suggest different mechanisms for iodine deficiency disorders of different aetiologies and hence the need for discrete approaches for their management.