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 l aboratory 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 phe notype/sex group at 4 weeks. In male rats, it became progressively low er (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 lea n male 4-week-old rats whereas it was lower (28%) in obese than in lea n females. It became progressively lower (39 and 49% at 12 and 16 week s 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 w eeks respectively) in obese than in lean rats. Serum TSH was not diffe rent 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 fe males, similar levels of serum TSH were maintained in both obese and l ean developing rats. Thyroid gland weight was not different in any phe notype/sex ,coup at 4 weeks. It became progressively lower (19 and 12% at 12 and 16 weeks respectively) in obese compared with lean male rat s, whereas no such difference was seen in female rats. The concentrati ons and total contents of T-4 and Tg in thyroid glands were not differ ent 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 wa s always lower in obese compared with lean male rats from 4 to 26 week s. 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 diff erences 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 w as 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 developmen tal and sex-related differences in the obese Zucker rat and suggest th at (1) the developing genetically obese Zucker rat becomes progressive ly pseudohypothyroid, as compared with the lean Zucker rat, (2) thyroi d metabolism is impaired more and earlier in male than in female obese rats, (3) the perturbation is not mainly the result of a decreased gl andular production of thyroid hormones, and (4) a dysfunction in perip heral thyroid metabolism as well as in the hypothalamo-pituitary axis may be involved in the perturbation of the thyroid function of obese r ats.