SFEBES2015 Poster Presentations Thyroid (59 abstracts)
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
Thyroid hormones increase foetal and adult metabolic rates, and, in adult tissues, increase mitochondrial biogenesis. Foetal tri-iodothyronine (T3) concentrations rise towards term in preparation for the increased postnatal energy demands but whether they affect mitochondrial development remains unknown. This study examined mitochondrial development in skeletal muscle of thyroid hormone deficient sheep foetuses near term.
At 105110 days (d) of gestation (term ~d145), 11 twin-bearing pregnant ewes were anaesthetised for foetal thyroidectomy (TX) and sham operation of the pairs. Foetal plasma and muscle samples were collected at d129 (n=6) or d143 (n=5) after maternal and foetal euthanasia. Citrate synthase (CS) activity was measured spectrophotometrically as an index of mitochondrial density, whilst abundance of electron transport chain (ETC) complexes I-IV and ATP-synthase was determined by western blotting to assess mitochondrial function, in foetal biceps femoris muscle. Plasma T3 was measured by radioimmunoassay. Data were analysed by two-way ANOVA with Tukeys post-hoc test.
At both ages, muscle CS activity was less in TX than control foetuses (Table). Foetal TX prevented the normal gestational increase in CS activity (Table). Combining all data, muscle CS activity correlated positively with foetal plasma T3 (r=0.749, n=22, P<0.0001). Relative to control muscle, complexes I and IV abundance was lower at d129, while ATP-synthase and all ETC complexes, except complex II, were less at d143 in TX muscle. However, when normalised to CS activity, muscle protein abundance of ATP-synthase was higher in TX than controls, at both ages (Table 1).
d129 | d143 | |||
Control | TX | Control | TX | |
CS activity μmol/min per mg protein | 0.169±0.016 | 0.069±0.007* | 0.439±0.036† | 0.108±0.008* |
ATP-synthase/ CS activity | 7.25±0.66 | 13.68±1.35* | 3.95±0.46 | 9.19±0.53*† |
Data are mean±S.E.M. *P<0.05, TX vs controls at same age or †P<0.05 d143 vs d129 with same treatment. |
Therefore, thyroid hormones are essential for the normal developmental increase in mitochondrial density and oxidative capacity in foetal skeletal muscle towards term.