Feedback regulation of TSH secretion in rats with hypothalamic lesions

Abstract

Regulation of the pituitary-thyroid axis was studied in rats with bilateral lesions in the paraventricular area of the hypothalamus. Following lesions, there was a persistent (up to 2 months) fall in levels of plasma protein-bound iodine and free thyroxine and pituitary TSH concentrations. Plasma TSH was 28.5 ± 3.6 mU/100 ml in intact animals; after lesions values fell below the limit of immunoassay (<10 mU/ 100 ml) in 7 of 9 animals. Following thyroidectomy, plasma TSH levels in hypothalamiclesioned rats increased more slowly than did controls. At 10 days after thyroidectomy plasma TSH levels in hypothalamic-lesioned rats were not detectably increased, while normals were significantly elevated. Forty days after thyroidectomy, rats with lesions had elevated TSH levels, but the response was significantly less than normal. To evaluate effects of hypothalamic lesions on pituitary sensitivity to feedback inhibition, thyroidectomized animals were treated for 9 days with graded doses of T4. Plasma free T4 concentrations of 0.94-0.98 ng/100 ml were achieved in normal and lesioned rats with T4 dosage of 0.5 ’g T4/100 g body wt/day. This level effectively suppressed plasma TSH levels in rats with lesions but had no suppressive action in thyroidectomized rats without lesions. These results indicate that lesions of the thyrotropic area increase the sensitivity of the pituitary to feedback inhibition by thyroid hormone. This effect is due presumably to a reduction in the amount of TRF which is delivered to the pituitary in hypothalamic-lesioned animals. © 1970 by The Endocrine Society.