TSH synthesis and release in the thyroidectomized rat: a) Effect of short- and long-term hypothyroidism.

Abstract

ABSTRACT Groups of surgically thyroidectomized (T) male rats were sacrificed at intervals during the period of 1 to 5 and 30 to 180 days after <UNK> Plasma T3, T4 and TSH levels and pituitary TSH content were measured by RIA. A drop of plasma T3 and T4 from normal to undetectable values occurred by day 3 post <UNK>. There was a progressive increase of plasma TSH from the normal value of 136 ± 14 ng/ml to 1623 ± 186 ng/ml (mean ± sem) at day 5 post T, reaching at 30 days a new plateau of 8618 ± 527 ng/ml. These levels remained unchanged up to 130 days post <UNK>. At 180 days, plasma TSH (4123 ± 991 ng/ml) fell significantly below the plateau level. Pituitary TSH content fell from the normal value of 80.9 ± 15.9 μg/mg to a nadir of 12.7 ± 1.4 μg/mg at day 4 post <UNK> and then slowly rose to 98.6 ± 5.9 μg/mg at 100 days, remaining at this level for another 30 days and finally declining significantly at 180 days post <UNK>. The rates of TSH release and synthesis were calculated using the metabolic clearance rates (MCR), determined from the curves of disappearance of injected [125I]-TSH by a non-compartmental analysis. The MCR values decreased, starting at 8 days after T, and reached about half the normal value from 30 days onwards (0.257 ± 0.03 to 0.144 ± 0.001 ml/min/100 g b.w.). The rate of TSH release was increased as early as the first day post <UNK>. A 6-fold increase was reached after 5 days and a new steady state of about 32-fold increase was attained within 1 month. TSH synthesis was also stimulated. However, it lagged behind the stimulation of the release for the first 4 days after <UNK>. The data indicate that: a) The depletion of thyroid hormones affects both synthesis and release of TSH. b) Under prolonged hypothyroidism TSH release and synthesis are in equilibrium, at a markedly enhanced rate. c) Very severe and prolonged hypothyroidism results in a decline in both pituitary and plasma TSH levels.