Effects of Propylthiouracil, Methimazole and Thyroidectomy on Liver and Plasma Proteins: Differential Response to Thyroxine

Abstract

Differential effects of propylthiouracil (PTU), methimazole (MMI) and thyroidectomy (Tx) on liver and plasma proteins have been studied in rats, some of which have been simultaneously treated with L-thyroxine (T4). Although the absolute liver weights were lower in all hypothyroid groups, the relative liver weights (g/100 g) were significantly higher in PTU and MMI groups, while in Tx group they were lower. T4 administration raised the absolute liver weights in all groups, even though there was no significant difference between relative weights in PTU and MMI groups. In Tx group, however, the relative weight was restored to control level. One of the constituents responsible for the increased relative liver weight was liver protein. The increased liver protein concentration (mg/g) was, however, not reflected in the synthesis rate which was uniformly low in all groups inspite of T4 therapy. Plasma albumin concentration was raised in hypothyroid rats which did not respond to T4 therapy. On the other hand, increased total plasma protein level was restored to normal. Relative 14C-glycine incorporation into albumin, fibrinogen, seromucoids and total proteins was reduced from 14 to 30%, 5.2 to 19% and 13 to 23% of control in PTU, MMI and Tx groups, respectively. Of these, only MMI and Tx groups appeared to be responsive to T4 therapy. Of all the protein fractions, fibrinogen synthesis was least affected by various treatments. To some extent these observations may be explained on the basis of altered general endocrine status and specific extra-thyroidal effects, rather than on the basis of thyroid status alone.

Differential Effects of Propylthiouracil, Methimazole and Thyroidectomy on Liver Ferritin

“…MMI appeared to be having negligible influence on ferritin synthesis, eventhough it increased the ferritin concentration. This may be partly a reflexion of increased liver weight and elevated liver mixed protein concentration observed by us earlier (Nadkarni et al, 1983).…”

“…It has now been well recognized that PTU and MMI have noticeable effects on extrathyroidal tissues, especially the liver (Nadkarni et al, 1983;Nadkarni et al, 1979;Nadkarni and Dèshpande, 1982;Nadkarni et al, 1979 a). Though PTU, MMI and thyroidectomy produce comparable degree of hypothyroidism, the general endocrine status of such rats is variable (John and Escobar, 1968;John et al, 1970).…”

“…The materials used and the treatments of rats are the same as reported by us earlier (Nadkarni et al, 1983). In lief, adult male Wistar rats (160-180 g) fed on 20% protein diet (Nadkami et al, 1979) were divided into four groups.…”

“…Plasma proteins and liver mixed proteins in such rats have been studied in detail. Subtle differences in these parameters and their differential response to exogenous-L-thyroxine (T4) have been observed (Nadkarni et al, 1983). These earlier studies have been confined to total mixed proteins and specific export proteins of hepatic origin (Nadkarni et al, 1983;Nadkarni and Samuel, 1973), rather than specific intracellular proteins.…”

“…Subtle differences in these parameters and their differential response to exogenous-L-thyroxine (T4) have been observed (Nadkarni et al, 1983). These earlier studies have been confined to total mixed proteins and specific export proteins of hepatic origin (Nadkarni et al, 1983;Nadkarni and Samuel, 1973), rather than specific intracellular proteins. Ferritin is a water-soluble, cytoplasmic ironstorage protein of mammalian tissues, found predominantly in the liver, spleen and bone marrow (Munro and Linder, 1978).…”