Differential effects of D- and L-isomers of triiodothyronine on pituitary TSH secretion and peripheral deiodinase activity in the rat.
The effects of D- and L-T3 were compared in male SK & F Wistar rats to define overall effects on the 'pituitary-thyroid-liver axis' at high doses. After in vivo administration of L-T3 (up to 1 mg/kg orally, or up to 0.1 mg/kg subcutaneously) serum TSH and T4 were decreased in a dose-related manner. Similarly, following in vivo exposure to L-T3, both basal and TRH-stimulated TSH output from isolated superfused pituitary glands was decreased, but only the latter was affected by direct in vitro exposure to L-T3.D-T3 had between 1% and 10% the activity of L-T3 in decreasing these parameters both in vivo and in vitro. In contrast, both enantiomers increased liver and kidney deiodinase activity to approximately the same extent, presumably as a compensatory response to clear hormone from the body. These observations indicate that, following treatment with L- or D-T3 by oral gavage for 14 days, the 'no effect' dose (i.e. the dose which did not significantly decrease serum TSH concentrations as compared with controls) for L-T3 was below 0.01 mg/kg whereas that for D-T3 was 0.1 mg/kg.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007453:Iodide Peroxidase / Q000032:analysis*; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013972:Thyrotropin / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D013974:Thyroxine / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*
D014284:Triiodothyronine; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D007453:Iodide Peroxidase; D013974:Thyroxine