The effect of basal hypothalamic isolation on pituitary-thyroid activity and the response to propylthiouracil.

Basal hypothalamic deafferentation extending from the posterior border of the optic chiasm to the mid-mammillary bodies resulted in depression of plasma TSH, thyroxine (T4), and triiodothyronine (T3) concentration to 50% of normal controls within 7 days. Administration of 0.15% propylthiouracil (PTU) in the diet form postoperative day 26 caused a pronounced drop in the plasma T3 level and a rise in plasma TSH level within two days in the control animals, but had little effect during this interval in the deafferented animals. After 12 days of PTU, plasma T3 and T4 concentrations had dropped to undetectable concentrations in the control animals but both were still detectable in the deafferented animals. After 25 days of PTU, plasms T4 and T3 levels were undetectable and plasma TSH levels were significantly elevated above normal in all animals. Thyroid hypertrophy at that time was as great in the deafferented as in the control rats, although plasma TSH concentration was 50% lower in the former. Administration of 0.1 mug/100 g BW TRH iv on postoperative day 37, when plasma T4 and T3 were undetectable in the controls but still present in the deafferented animals, produced an equally high concentration of plasma TSH in all animals. We interpret these data to support the concepts that: 1) a major source of neural drive of that TRH which stimulates the secretion of TSH by the adenohypophysis lies outside the medial basal hypothalamus, 2) a decrease in TRH reaching the adenohypophysis causes a lower setting of the "thyrostat" sensitive to the concentration of circulating thyroid hormone, and 3) increased TSH secretion and resultant goitrogenesis is delayed in animals with impaired TRH secretion because of the slower rate of secretion of thyroid hormone than in intact controls and the longer time thus required to markedly reduce the concentration of circulating thyroid hormone.