Tessy,Maliekal T; Sudha, B; Paulose,C S(Department of Biotechnology, February 14, 1997)
[+]
[-]
Abstract:
The role of thyroid hormones in DNA synthesis and in the activity of Thymidille
kinase (TK), a key regulatory enzyme of DNA synthesis was studied in proliferating
hepatocytes in vivo. Liver regeneration after partial hepatectomy was used as a
model for controlled cell division in rats having different thyroid status - euthyroid,
hypothyroid and 3,3',5'-triiodo-L-thyronine (T))-heated hypothyroid. Partial
hepatectomy caused a significant elevation of DNA synthesis (p<0.01) in all the three
groups compared to their sham-operated counterparts. Hypothyroid liepatectomised
animals showed significantly lower (p<0.01) level of DNA synthesis than euthyroid
hepatectomised animals. A single subcutaneous close of 1'3 to hypothyroid shamoperated
animals resulted in a significant increase (p<0.01) of DNA synthesis in the
intact liver. 17tis was comparable to the level of DNA synthesis occurring in
regenerating liver of euthyroid animals. In hypothyroid hepatectomised animals, "1'3
showed an additive effect on l)NA synthesis and this group exhibited maximum level
of DNA synthesis (p<0.0I ). Studies of the kinetic parameters of TK show that the
Michelis-Menten constant, (K111) of TK for thymidine was altered by the thyroid
status. K11 increased significantly (p<0.01) in untreated hypothyroid animals when
compared to the euthyroid rats. '13 treatment of hypothyroid animals reversed this
effect and this group showed the lowest value for K111 (p<0.01). Thus our results
indicate that thyroid hormones can influence DNA synthesis during liver regeneration
and they may regulate the activity of enzymes such as 17rymidine kinase which are
important for DNA synthesis and hence cell division.