Date of Award


Degree Type


Degree Name

Doctor of Philosophy


Male Sprague-Dawley rats were injected with 300{dollar}\mu{dollar}g/kg body weight of Triiodo-L-thyronine (T{dollar}\sb3{dollar}) and L-thyroxine (T{dollar}\sb4{dollar}) on alternate days over a 28-day treatment period. Thyrotoxicosis was confirmed by increased serum T{dollar}\sb3{dollar} levels and a pronounced ventricular hypertrophy (p {dollar}\le{dollar} 0.05 after 5 days). The effects of thyroid hormone on isometric contractile properties of the slow-twitch soleus muscle were studied in situ after 2, 5, 7, 15, 21 or 28 days. Time to peak tension (TPT) and one half relaxation time (1/2 RT) were significantly reduced after 5 days (T-5, p {dollar}\le{dollar} 0.05) and reached 56.7% and 51.1% of age-matched control values at T-28. This abbreviated twitch response increased the fusion required for the summation, and force production at sub-maximal stimulation frequencies was reduced.;The Ca{dollar}\sp{lcub}2+{rcub}{dollar}-activated myosin ATPase activity of experimental muscles assayed at pH 9.8 increased to 400% of control activity at T-28. A further indication of myosin transformation was a decrease in the complement of slow myosin light chains (MLC1{dollar}\sb{lcub}\rm s{rcub}{dollar} and 2{dollar}\sb{lcub}\rm s{rcub}{dollar}) and a concomitant increase in fast myosin light chains (MLC1{dollar}\sb{lcub}\rm f{rcub}{dollar}, 2{dollar}\sb{lcub}\rm f{rcub}{dollar} and 3{dollar}\sb{lcub}\rm f{rcub}{dollar}) (p {dollar}\le{dollar} 0.05 at T-15).;Myosin heavy chain (MHC) composition was analyzed with four monooclonal antibodies (Mabs) which were screened for their specificity to rat MHC isoforms. Immunoblot and ELISA analyses demonstrated a reduction of type I (slow) MHC in experimental muscles (p {dollar}\le{dollar} 0.05 at T-5). The embryonic MHC was not re-expressed. A novel MHC isoform (IIB/IIX) appeared by T-5. Immunofingerprinting experiments suggested that this was the IIB rather than the IIX MHC isoform.;Enzyme histochemistry and immunocytochemistry were used to assess whether MHC transformation was uniform or fibre-specific. Type I MHC was reduced in all type I fibres but was never completely eliminated. The number of fibres expressing type II MHC increased to reach 90.3 {dollar}\pm{dollar} 1.6% at T-28 but a sub-population of fibres (10%) remained unaffected. De novo expression of IIB MHC occurred initially in pre-existing IIA fibres, and was still restricted to 31.4 {dollar}\pm{dollar} 4.4% of the fibre population at T-28.;This study demonstrated that changes in MHC composition occurred rapidly but were probably of insufficient magnitude to account for the initial changes in contractile function. The differential response of individual fibres to thyroid hormone may result from a compromised neuromuscular interaction, or may stem from their developmental origin which could limit their adaptive range.



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