Endocrinology, Vol 100, 1186-1191, Copyright © 1977 by Endocrine Society
The mechanism of damping of the serum thyroxine and triidothyronine levels caused by increasing thyrotropin dosage in mice
M Gafni, C Saddok, N Sirkis and J Gross
The time course of the effect of bovine TSH (bTSH) on serum concentrations
of thyroxine (T4) and triiodothyronine (T3) was measured in the normal
mouse. The basal, unstimulated levels were 3.2+/-1.1 mug/100 ml T4 and
104+/-25 ng/100 ml T3 (mean+/-SD). With doses of bTSH from 0.5 to 100 mU
the peak levels of the thyroid hormones were only 2.6 and 1.8 times the
basal level for T4 and T3, respectively. With increasing doses of bTSH
there was a proportional prolongation of the increased serum levels of
thyroid hormones, i.e., about 2 h for 0.5mU to 12 h for 100 mU TSH. The
integrated response with time was linearly related to the log dose. This
would suggest a control mechanism which prevents excessive concentration of
thyroid hormones in the serum. This pattern of response to TSH differs
somewhat from that obtained by following radioiodine release in the
McKenzie type bio-assay. To avoid the problems of changing blood
concentrations of thyroid hormones and TSH, the release of T4 and T3 from
the mouse thyroid was measured in vitro. The secretion increased with bTSH
concentrations in the range of 0.02-0.8 mU/ml for T4 and 0.02-0.4 mU/ml for
T3. The maximal response was 8.8+/-0.5 ng T4/3h/thyroid and 3.6+/-0.3 ng
T3/3h/thyroid as against the basal secretion of 2.4+/-0.2ng T4 and
0.8+/-0.1 ng T3 (mean+/-SEM). Further in crease in bTSH concentration was
associated with a decreased rate of thyroid hormone release. Thyroidal cAMP
accumulation was enhanced with increasing bTSH concentration, even when
there was a decrease in secretion. The dichotomy in the dose-response
pattern between the two parameters indicated that the effect of high TSH
concentrations on the release was induced at a step beyond cAMP
accumulation. This was corroborated by the similar pattern of release
induced by increasing concentration of DBcAMP.These findings indicate the
existence of an intrathyroidal autoregulatory mechanism which prevents
excess increase of thyroid hormone levels in the blood.
