Aspects of Chronic Oral Treatment with Thyrotropin-Releasing Hormone: The Hypothalamic-Pituitary-Thyroid Axis in Rats

Abstract

The effects of 16 days of oral treatment with thyrotropin-releasing hormone (TRH, 1 mg/24 h) on serum levels of thyrotropin (TSH), thyroxine (T₄) and triiodothyronine (T3) and the kinetics of TRH in the blood were studied in normal rats. A second group of animals served as controls. TRH was dissolved by sonification (10 mg/l) and was stable in tap water. TRH was measured by a radioimmunoassay procedure (normal range: 20–80 pmol/l, antiserum K2B9 1:120,000 final dilution). An increase in basal TSH (7,200 ± 440 ng/l, mean ± SD) was found after 2 days of treatment (11,420 ± 810 ng/l), but a significant increase was observed after 5 days of treatment (12,530 ± 640 ng/l, p < 0.001). T₄ serum concentrations remained in the normal range during the entire period of study, whereas T₃serum concentrations (0.76 ± 0.1 µg/l) were increased to 1.22 ± 0.2 µg/l on day 5 (p < 0.001). A subsequent decline of TSH, T₄ and T₃ up to the end of the study was observed. TRH_max concentrations were registered on day 5 (790 ± 24 pmol/l). The mean value of TRH_max was 723 ± 34 pmol/l. To improve the stability of TRH in tap water, 1-ml samples of drinking water with dissolved TRH were measured. The mean TRH concentration in drinking water was 73 ± 1.5% (SD). No significant correlations were found between the area under the curve of TSH (184,340 ng·l^–1·24 h) and that of TRH (14,954 pmol·l^–1·24 h). These findings suggest that (1) chronic treatment with oral TRH cannot induce hyperthyroidism in rats, (2) oral TRH is absorbed when dissolved in tap water where it is stable and (3) the enzymatic process of TRH degradation is saturated at high doses of the peptide used in this study. Chronic treatment with oral TRH is a useful model to study the pituitary reserves in relation to TRH blood levels.

Thyroid hormone deficiency alters expression of acid-base transporters in rat kidney

“…fT 4 levels were reduced ϳ10-fold, and TSH levels increased similar to what has been described in this and similar models of hypothyroidism (11,35,41). A second group of animals was treated with methimazole but with L-thyroxine substituted and showed normal fT 4 and TSH levels as described in various rat models (15,35). This group served as the euthyroid control group (EU).…”