title: Daily variations in type II iodothyronine deiodinase activity in the rat brain as controlled by the biological clock.
abstract: Type II deiodinase (D2) plays a key role in regulating thyroid hormone-dependent processes in, among others, the central nervous system (CNS) by accelerating the intracellular conversion of T4 into active T3. Just like the well-known daily rhythm of the hormones of the hypothalamo-pituitary-thyroid axis, D2 activity also appears to show daily variations. However, the mechanisms involved in generating these daily variations, especially in the CNS, are not known. Therefore, we decided to investigate the role the master biological clock, located in the hypothalamus, plays with respect to D2 activity in the rat CNS as well as the role of one of its main hormonal outputs, i.e. plasma corticosterone. D2 activity showed a significant daily rhythm in the pineal and pituitary gland as well as hypothalamic and cortical brain tissue, albeit with a different timing of its acrophase in the different tissues. Ablation of the biological clock abolished the daily variations of D2 activity in all four tissues studied. The main effect of the knockout of the suprachiasmatic nuclei (SCN) was a reduction of nocturnal peak levels in D2 activity. Moreover, contrary to previous observations in SCN-intact animals, in SCN-lesioned animals, the decreased levels of D2 activity are accompanied by decreased plasma levels of the thyroid hormones, suggesting that the SCN separately stimulates D2 activity as well as the hypothalamo-pituitary-thyroid axis.
authors.affiliation: Netherlands Institute for Brain Research, Department of Endocrinology and Metabolism, 1105 AZ Amsterdam, The Netherlands. a.kalsbeek@nih.knaw.nl
authors.forename: Andries
authors.initials: A
authors.lastname: Kalsbeek
authors.forename: Ruud M
authors.initials: RM
authors.lastname: Buijs
authors.forename: Rosalinde
authors.initials: R
authors.lastname: van Schaik
authors.forename: Ellen
authors.initials: E
authors.lastname: Kaptein
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
authors.forename: Behrouz Zandieh
authors.initials: BZ
authors.lastname: Doulabi
authors.forename: Eric
authors.initials: E
authors.lastname: Fliers
mesh_terms: D000305:Adrenal Cortex Hormones / Q000097:blood; D000818:Animals; D001683:Biological Clocks; D001921:Brain / Q000201:enzymology*; D002490:Central Nervous System / Q000378:metabolism / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D007453:Iodide Peroxidase / Q000378:metabolism*; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013493:Suprachiasmatic Nucleus / Q000201:enzymology*; D013963:Thyroid Hormones / Q000378:metabolism; D013974:Thyroxine / Q000378:metabolism; D013997:Time Factors; D014284:Triiodothyronine / Q000378:metabolism; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D000305:Adrenal Cortex Hormones; D003345:Corticosterone; D007453:Iodide Peroxidase; D013963:Thyroid Hormones; D013974:Thyroxine; D014284:Triiodothyronine; D000097564:Iodothyronine Deiodinase Type II