The effect of thyroid hormone on mitochondrial biogenesis and cellular hyperplasia.

The purpose of this investigation was to study the effects of thyroid hormone treatment on the levels of DNA, RNA, and protein in hepatocytes and hepatocyte mitochondria. A preliminary investigation was conducted to establish an effective dosage of thyroid hormone. Male Sprague-Dawley rats were given daily subcutaneous injections of L-thyroxine (20, 40, or 60 micrograms/100 g body weight) and the following determinations made over a 14-day period: (1) body weight; (2) total body respiration; and (3) the activities of the mitochondrial enzymes, succinate dehydrogenase and alpha-glycerophosphate dehydrogenase. Dosages of 20 and 40 micrograms L-thyroxine/200 g body weight produced significant stimulation of (a) total body respiration and (b) succinate dehydrogenase and alpha-glycerophosphate dehydrogenase activities without any inhibitory effects on normal weight gain of the animals. Injections of 40 micrograms L-thyroxine/100 g body weight were utilized for subsequent studies. Hepatic DNA levels of treated animals were greater than age-paired control values by 28% on day 7 and 43% by day 14. Total liver RNA levels of thyroid-treated animals were 17% greater than those of controls by day 7 and 47% greater by day 14. Analyses were also performed on mitochondria quantitatively collected by rate zonal centrifugation. Total liver mitochondrial DNA levels in thyroid-treated animals were greater than age-paired controls by 79% at 7 days but only 67% at 14 days since a small gain occurred in control animals and no further increase occurred in treated rats during the second week. Mitochondrial RNA and protein from treated livers were 26% and 16% higher, respectively, than age-paired controls at day 7 and 40% and 58% higher, respectively, at day 14. The results of this study indicated that thyroid hormone treatment produces hyperplasia and an increase in mitochondrial number and mass in rat liver.