Altered Pituitary-Thyroid Function in the Brattleboro Rat with Diabetes Insipidus*

Abstract

To determine the roles of vasopressin in the regulation of the pituitary-thyroid axis, we studied this axis in vasopressin-deficient Brattleboro rats with diabetes insipidus. When plasma TSH, T₃, and T₄ concentrations were determined by RIA, it was found that plasma TSH levels were increased by 100–170%, and T₃ levels were lowered by about 20% in the homozygous (DI) and heterozygous (HZ) Brattleboro rats. The plasma T₄ level decreased by about 20% in DI rats, whereas its level in HZ rats was similar to the control level. TRH (250 ng/ 100 g BW, iv) increased plasma TSH levels at 10 and 20 min in all three groups, but the TSH response to TRH in DI and HZ rats was significantly greater than that in the control rats. Continuous administration of desamino-D-arginine vasopressin (48 ng/day for 7 days, sc) normalized urine volume and osmolality in DI rats, but did not affect the abnormalities in the pituitary-thyroid axis. The same dose of DDAVP in HZ anials significantly decreased urine volume and increased osmolality, and restored normal basal and TRH-induced levels of plasma TSH without altering plasma levels of T₃ and T₄. There was a significant thyroidal response to TSH (100 mU/100 g BW, iv) of increased plasma T₃ and T₄ concentrations in the control, but not in DI and HZ rats. There were no significant differences in removal constants, volumes of distribution, or MCRs of plasma T₄ or TSH among the control, DI, and HZ animals. These results suggest that the abnormalities in the hypothalmo-pituitary-thyroid axis of the Brattleboro rats are independent of the disruptions in water balance resulting from the lack of vasopressin. Instead, the abnormalities are, at least in part, due to the reduced sensitivity of the thyroid gland to TSH, resulting in decreased circulating levels of thyroid hormones, which may in turn enhance pituitary secretion of TSH.