Differential effects of methimazole and dexamethasone in avian muscular dystrophy.
We showed previously that thyroid antagonists and glucocorticoids partially alleviated the impaired righting ability and abnormally high levels of plasma creatine kinase activity in genetically dystrophic chicks. The goals of the present study were: (1) to ascertain whether the beneficial effects of methimazole (MMI; thyroid antagonist) on muscle function and plasma creatine kinase (CK) activity in dystrophic chickens are correlated with significant reduction in plasma triiodothyronine (T3) and thyroxine (T4); (2) to assess whether the MMI-induced thyroid changes are accompanied by increased plasma corticosterone level and/or changes in muscle glucocorticoid receptors which might account partially for the beneficial effects of MMI; and (3) to determine if plasma T3 and T4 are reduced in dexamethasone (DEX) treated dystrophic chickens which might account at least partially for the beneficial effects of DEX (a potent glucocorticoid) on avian dystrophy. The data show that beneficial effects of MMI are associated with reduced plasma levels of thyroid hormones and increased circulating levels of corticosterone. In addition, DEX actually increases plasma T3 levels. These differential effects indicate that reduced plasma thyroid hormone levels do not represent a common mechanism of beneficial drug effects in avian muscular dystrophy. On the other hand, elevated plasma glucocorticoid levels accompany the beneficial effects of both severe hypothyroidism and DEX treatment. The data also show that MMI induces down-regulation of muscle cytosolic glucocorticoid receptors which are higher than normal in dystrophic muscles.
Sabeur
K
K
Dept. of Physical Medicine and Rehabilitation, School of Medicine, University of California, Davis 95616.
King
D B
DB
Entrikin
R K
RK
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002645:Chickens; D003345:Corticosterone / Q000097:blood; D003402:Creatine Kinase / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology*; D008297:Male; D008713:Methimazole / Q000494:pharmacology*; D009132:Muscles / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D009137:Muscular Dystrophy, Animal / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D011965:Receptors, Glucocorticoid; D014284:Triiodothyronine; D008713:Methimazole; D003907:Dexamethasone; D003402:Creatine Kinase; D013974:Thyroxine; D003345:Corticosterone