DEVELOPMENT OF THYROXINE TYPE-II DEIODINASE ACTIVITY IN BRAINS OF ZUCKER RATS

The present study was undertaken to determine whether the capacity for 3,5,3',5'-tetraiodothyronine (T-4) conversion into 3,5,3'-tri-iodothy ronine (T-3), as measured by the activity of thyroxine type II 5'-mono deiodinase (T-4-5'D), was altered in the brains of young Zucker fa/fa rats during the period of intense maturation of the central nervous sy stem (i.e. from 10 to 20 days of life). From 7 to 14 days of age, no d ifference in brain T-4-5'D activity could be detected between lean and pre-obese rats; serum free T-4 was not affected by the fa gene. Durin g the suckling to weaning transition, T-4-5'D reached a plateau in bra ins of lean rats, while it increased by 50% in brains of preobese rats ; concurrently, serum free T-4 increased in Fa/fa rats, whereas it did not change in fa/fa rats. The increased capacity for conversion of T- 4 into T-3 observed in brains of pre-obese compared with lean rats cou ld not be ascribed to a variation in the amount of T-4-5'D, since V-ma x did not differ between the two genotypes; however, it could be total ly accounted for by an increased affinity of the enzyme for T-4. This change may represent an adaptive response to low serum free T-4 in ord er to maintain the cerebral T-3 concentration in pre-obese rats. These results show that the alteration in T-4 metabolism in brains of fa/fa rats is not an early event and thus cannot interfere with maturation of the central nervous system. However, the decreased serum free T-4 w hich was observed in pre-obese rats after suckling might play a second ary role in development of this genetic obesity.