The effect of iodine deficiency and propylthiouracil on the hypothalamo–pituitary–thyroid axis in the neonatal rat

Abstract

The effect of chronic propylthiouracil (PTU) and low iodide diet (LID) on the development of the hypothalamo–pituitary–thyroid axis in the rat has been studied. Pregnant and neonatal rats received 0.05% PTU in their drinking water or LID (distilled water and LID: Teklad Mills, Madison, Wisconsin). Control animals received tap water and Purina rat chow ad libitum. Hypothalamic thyrotropin-releasing hormone (TRH), pituitary and serum thyroid-stimulating hormone (THS), and serum thyroxine (T₄) and triiodothyronine (T₃) were measured by specific double-antibody radioimmunoassay. Both PTU- and LID-exposed animals had low hypothalamic TRH concentrations at 1 day and a rapid rise to peak levels of 2.4 ± 0.4 pg/μg protein (mean ± SEM) between 12 and 24 days in the PTU animals and 3.2 ± 0.4 pg/μg protein between 12 and 18 days in the LID rats. Hypothalamic TRH concentrations remained relatively stable in the PTU animals, whereas in the LID rats, after a brief but significant decline from 24 to 28 days, hypothalamic TRH concentrations rose to the highest values observed at 57 days (3.9 ± 0.5 pg/μg protein). Both groups of animals had elevated serum TSH levels at 1 day, with higher values seen in the PTU group (p < 0.01), and both showed a rapid rise at 12 days. Thereafter, serum TSH concentrations remained high in the PTU rats but declined to stable, albeit elevated, levels by 24 days (1260 ± 140 ng/ml) in the LID animals. Hypothyroidism was confirmed in the PTU animals by undetectable T₄ and reduced T₃ concentrations. In the LID rats, serum T₄ concentrations rose from undetectable levels at 1 day to stable values by 32 days (2.18 ± 0.13 μg/dl). Serum T₃ rose to peak values of 157.0 ± 6.9 ng/dl at 32 days and was elevated at all times after 12 days. These data suggest that chronic exposure to PTU or LID results in a marked derangement of the ontogenetic pattern of the hypothalamo–pituitary–thyroid axis. In addition, neonatal rats exposed to LID appear to respond appropriately by preferential T₃ production.