Effects of the synthetic liver X receptor agonist T0901317 on the growth hormone and thyroid hormone axes in male rats.
Liver X receptors (LXRs), activated by oxysterols, play an important role in the regulation of lipid and glucose metabolism, which is also markedly dependent on thyroid hormone and growth hormone (GH) status. Here, we investigated how a 1-week exposure to the synthetic LXR agonist T0901317 affected GH secretion and thyroid hormone status in male rats. While the pulse frequency of GH secretion was marginally affected there was a highly significant decrease in the triiodo-L-thyronine/thyroxine (T3/T4) ratio in plasma. This effect was associated with decreased expression of deiodinase 1 (DIO1) and 2 (DIO2) mRNA in the liver and thyroid gland, respectively. Expression of sterol regulatory element binding protein-1c (SREBP-1c), the hallmark of stimulated lipogenesis, was markedly increased in both thyroid and pituitary implying that protracted pharmacological LXR activation may promote lipid accumulation in these endocrine tissues. These findings suggest that attention must be given to pituitary hormone dependent axes when developing therapeutic strategies based on agonism of the LXRs, e.g. for treatment of atherosclerosis.
Davies
Jeffrey S
JS
School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3US, UK.
Kotokorpi
Pia
P
Lindahl
Ulrika
U
Oscarsson
Jan
J
Wells
Timothy
T
Mode
Agneta
A
D000818:Animals; D004268:DNA-Binding Proteins / Q000819:agonists*; D004032:Diet; D004435:Eating / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D013006:Growth Hormone / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D006845:Hydrocarbons, Fluorinated; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008055:Lipids / Q000096:biosynthesis; D000071518:Liver X Receptors; D008297:Male; D009929:Organ Size / Q000187:drug effects; D057093:Orphan Nuclear Receptors; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D013256:Steroids / Q000097:blood; D013449:Sulfonamides / Q000494:pharmacology*; D013963:Thyroid Hormones / Q000097:blood / Q000378:metabolism*; D013972:Thyrotropin / Q000097:blood; D014280:Triglycerides / Q000097:blood; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D004268:DNA-Binding Proteins; D013006:Growth Hormone; D006845:Hydrocarbons, Fluorinated; D008055:Lipids; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D012313:RNA; D018160:Receptors, Cytoplasmic and Nuclear; D013256:Steroids; D013449:Sulfonamides; D013963:Thyroid Hormones; D013972:Thyrotropin; D014280:Triglycerides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides