CHANGES IN THYROID-HORMONE AND THYROTROPIN IN THE SERUM AND THYROID-GLANDS OF DEVELOPING GENETICALLY-OBESE MALE AND FEMALE ZUCKER RATS

In a first experiment, serum thyroxine (T-4), 3,5,3'-triiodothyronine (T-3) and thyrotrophin (TSH) concentrations as well as thyroid gland T-4 and T-3 contents were measured in developing lean and obese Zucker male and female rats of 4-16 weeks of age. The rats were bred in our laboratory and always treated in sex-matched pairs of one lean and one obese rat from the same litter. Serum T-4 was not different in any phenotype/sex group at 4 weeks. In male rats, it became progressively lower (27 and 37% at 12 and 16 weeks respectively) in obese than in lean rats. In females, similar levels of serum T-4 were maintained in both obese and lean developing rats. Serum T-3 was Similar in obese and lean male 4-week-old rats whereas it was lower (28%) in obese than in lean females. It became progressively lower (39 and 49% at 12 and 16 weeks respectively) in obese than in lean developing male rats. In females, lower levels of serum T-3 were maintained (25 and 43% at 12 and 16 weeks respectively) in obese than in lean rats. Serum TSH was not different in any phenotype/sex group at 4 weeks. It rose in both obese and lean male rats with age, but became progressively lower (33 and 23% at 12 and 16 weeks respectively) in obese compared with lean rats. In females, similar levels of serum TSH were maintained in both obese and lean developing rats. Thyroid gland weight was not different in any phenotype/sex ,coup at 4 weeks. It became progressively lower (19 and 12% at 12 and 16 weeks respectively) in obese compared with lean male rats, whereas no such difference was seen in female rats. The concentrations and total contents of T-4 and Tg in thyroid glands were not different between obese and lean rats both in males and females. The thyroid T-3/T-4 ratio was similar in obese and lean female rats whereas it was always lower in obese compared with lean male rats from 4 to 26 weeks. In a second experiment, serum T-4, T-3, free T-3 (FT3), reverse T-3 (rT(3)) and TSH concentrations were determined in 14-week-old female Zucker rats purchased from a commercial laboratory. There were no differences between obese and lean rat serum levels of T-4 and TSH. Serum rT(3) was lower (20%) in obese than in lean rats, but the difference was not significant. Serum T-3 and FT3 were lower in obese female rats than in lean ones, the differences being about 20 and 22% for T3( )and FT4 respectively. These data provide new information about developmental and sex-related differences in the obese Zucker rat and suggest that (1) the developing genetically obese Zucker rat becomes progressively pseudohypothyroid, as compared with the lean Zucker rat, (2) thyroid metabolism is impaired more and earlier in male than in female obese rats, (3) the perturbation is not mainly the result of a decreased glandular production of thyroid hormones, and (4) a dysfunction in peripheral thyroid metabolism as well as in the hypothalamo-pituitary axis may be involved in the perturbation of the thyroid function of obese rats.