Suppression of hypothalamic deiodinase type II activity blunts TRH mRNA decline during fasting.
Fasting is characterized by disrupted thyroid feedback, with suppressed levels of thyroid hormones and paraventricular thyrotropin releasing hormone (TRH). We found that third ventricle administration of the deiodinase inhibitor, iopanoic acid, dose-dependently reduced deiodinase type II (DII) activity selectively in the hypothalamus. This suppression of DII by iopanoic acid during fasting prevented elevated DII activity and blunted the decline in hypothalamic TRH mRNA levels. Because fasting-induced elevation in hypothalamic DII activity is paralleled by increased hypothalamic T3 concentration, our study suggests that T3 formation by DII in the hypothalamus is the cause of disrupted thyroid feedback during fasting.
Coppola
Anna
A
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar St. FMB 339, New Haven, CT 06520, USA.
Hughes
Jeniter
J
Esposito
Emanuela
E
Schiavo
Luigi
L
Meli
Rosaria
R
Diano
Sabrina
S
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005215:Fasting; D025461:Feedback, Physiological; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D017403:In Situ Hybridization; D007453:Iodide Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007480:Iopanoic Acid / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013973:Thyrotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism
D012333:RNA, Messenger; D014284:Triiodothyronine; D013973:Thyrotropin-Releasing Hormone; D007453:Iodide Peroxidase; D007480:Iopanoic Acid