Sidney H. Ingbar

Divergent responses by human and mouse thyroids to human chorionic gonadotropin in vitro

hCG is a known stimulator of mouse thyroid in vivo. Studies were therefore performed to ascertain whether the thyroid-stimulating activity of hCG in the mouse could also be demonstrated by the in vitro techniques that had failed to show any activity of hCG in the human thyroid. When labeled with 125I and incubated at 22 degrees C in 20 mM Tris-0.5% bovine serum albumin (Tris-BSA), pH 7.45, with increasing concentrations (70-300 micrograms protein/ml) of a mouse thyroid fraction, a purified hCG preparation [( 125I]hCG) showed 5-12% specific binding. In contrast, its binding to a human thyroid particulate fraction, over the same range of protein concentrations, did not exceed 1%. When similar studies were performed at 37 degrees C in 10 mM Tris-50 mM NaCl-0.5% BSA, pH 7.45, [125I]hCG showed no detectable binding either to the human or the mouse thyroid fractions. At concentrations ranging from 1 to 20 mIU/ml (0.9-18 X 10(-9) M), bTSH stimulated cAMP release from human thyroid slices into the medium in a dose-dependent manner. In contrast, hCG concentrations from 10(3) to 10(4) IU/ml (2-20 X 10(-6) M) were without effect on cAMP release. bTSH, at concentrations of 4.5 and 9.0 mIU/ml (4 and 8 X 10(-9)M), stimulated cAMP release from the mouse thyroid, producing in the medium approximately 11- and 28-fold increases in cAMP concentration. hCG also stimulated cAMP release from the mouse thyroid, the increases being approximately 2.3- and 1.8-fold, in the presence of 2270 and 4540 IU/ml (4.5 and 9.0 X 10(-6) M), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Aging on Thyroid Economy in Man

ABSTRACT: The effects of aging on the thyroid are discussed under the headings of metabolic indices, thyroid function, hormone production, blood concentration, and thyroregulatory mechanisms. Possibly elderly men differ from elderly women with regard to thyroid economy, but the available data are too few and contradictory to permit drawing firm inferences about the effects of aging.

Interactions of bovine thyrotropin and human chorionic gonadotropin with adenylate cyclase in bovine thyroid membranes.

Previous studies have shown that crude preparations of human chorionic gonadotropin bind to bovine thyroid membranes, displace 125I-labeled bovine thyrotropin therefrom, and are weak agonists therein with respect to the activation of adenylate cyclase. The present studies reveal that concentrations of chorionic gonadotropin sufficient to elicit a maximal agonistic response of adenylate cyclase are strongly antagonistic to the stimulatory action of bovine thyrotropin in the thyroid membrane system. This effect is reminiscent of the inhibitory effects of crude human chorionic gonadotropin on other extragonadal tissues in vitro, and, like them, appears to be mediated by some factor(s) other than human chorionic gonadotropin itself, since highly purified human chorionic gonadotropin was without effect.

Factors determining the differential tissue response of Na/K-ATPase to thyroid hormone in the neonatal rat.

The concentration of ouabain binding sites (OBS), a measure of the abundance of sodium/potassium-dependent ATPase (Na/K-ATPase), was measured in cerebral cortex (CC), cerebellum (CBL), brown adipose tissue (BAT), and heart of neonatal rats with congenital hypothyroidism. In euthyroid rats, the concentration of OBS was 50- to 100-fold greater in the nervous tissue than in the nonnervous tissue. Congenital hypothyroidism resulted in a significant reduction in the number of OBS in all four tissues. Although in absolute terms (pmol/mg protein) the reduction was greater in the nervous tissues, in relative terms it was much greater in the nonnervous tissues. The restoration of OBS concentration was much more sensitive to T4 in CC, CBL, and BAT than in heart. In contrast, the response of OBS concentration to T3 in hypothyroid rats was greater in the heart, followed by the BAT and CBL, being minimal in CC. The sensitivity to T4 replacement correlated with the degree of the stimulation of the type II 5deiodinase (5D-II) by hypothyroidism, whereas the response to exogenous T3 correlated with the fraction of the tissue T3 that derives from plasma T3 and inversely with the plasma T3 concentration required to saturate 50% of the nuclear receptors as reported in previous studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of variations in acute and chronic iodine intake on the accumulation and metabolism of [35S]propylthiouracil by the rat thyroid gland☆

Studies were performed to ascertain the effect of varying levels of chronic iodine intake and varying doses of iodide [0.002–100 μmoles KI/100 g body weight (BW)] given acutely on the rat thyroid metabolism of [35S]PTU (8.76 μmoles/kg BW). With variations in both acute and chronic iodine intake, as much as four-fold changes in the thyroid content of total 35S and unchanged [35S]PTU were observed. In the low, normal and high chronic iodine intake groups increasing doses of iodide given acutely produced a biphasic response in the thyroid accumulation of total 35S and unchanged [35S]PTU. In each of the three chronic iodine intake groups, increasing iodide doses up to 0.1 μmoles/100 g BW were associated with an increase in total 35S and unchanged [35S]PTU. At this level of acute iodide dosage, the increase averaged 45% (P < 0.01). Following acute iodide doses greater than 0.1 and up to 5.0 μmoles/100 g BW, the mean total 35S and unchanged [35S]PTU decreased to levels significantly (P < 0.001) lower than those at the peaks. Greater doses of iodide (up to 100 μmoles/100 g BW) produced no consistent further change in the thyroid content of total 35S or unchanged [35S]PTU. Irrespective of the acute iodide dose, the higher the level of chronic iodide intake, the higher the thyroid accumulation of total 35S and the lower the overall mean percentage of total 35S present as unchanged [35S]PTU. As would have been expected, increasing acute doses of iodide were associated with progressive decreases in thyroid: serum iodide concentration gradients, and the dose of acute iodide required to induce an acute Wolff-Chaikoff effect was greater the higher the level of chronic iodine intake. No correlation was evident, however, between the effects of acute doses of iodide on aspects of intrathyroid iodine metabolism and their effect on the thyroid metabolism of [35S]PTU.

Effect of variations in acute and chronic iodine intake on the accumulation and metabolism of [35S]methimazole by the rat thyroid gland: Differences from [35S]propylthiouracil

Abstract Studies were performed to ascertain the effect of various levels of chronic iodine intake and varying doses of iodide [0.002–100 μmoles KI/100 g body weight (BW)] given acutely on the rat thyroid metabolism of [ 35 S]methimazole ([ 35 S]MMI, 8.76 μmoles/kg BW). Variations in both acute and chronic iodine intake were associated with as much as four-fold changes in thyroid levels of total 35 S and unchanged [ 35 S]MMI. Chronic low iodine intake resulted in a considerable reduction in the thyroid uptake of [ 35 S]MMI (40% decrease) from high or normal chronic iodine intake. Unlike [ 35 S]PTU studies, the effect of increasing acute iodide dosage produced a biphasic response in the thyroid uptake of [ 35 S]MMI only in low chronic iodine intake. In these animals 0.1 μmoles KI/100 g BW produced the maximum uptake of [ 35 S]MMI (300% increase) but had no effect on high or normal chronic iodine intake. In these latter groups of rats, thyroidal total 35 S increased to plateau levels with increasing acute iodide dosage in the range of 0.1–1 μmoles/100 g BW which were unaffected by increased iodide up to 100 μmoles/100 g BW. In low chronic iodine intake rats also, the thyroid 35 S level seen at 1 μmole/100 g was unaffected by increased iodide dosage up to 100 μmoles/100 g. The steady thyroid 35 S levels seen in this acute iodide dose range in low, normal and high chronic iodine rats were 100, 70 and 110% respectively greater than their control values. Unlike [ 35 S]PTU studies, in general, an increase in thyroid total 35 S achieved by varying acute or chronic iodine intake was found to be associated with a large increase in the percentage thyroid 35 S occurring as free inorganic sulphate with a consequent effect on thyroid unchanged [ 35 S]MMI. In chronic low iodine intake animals treated with acute radioidide, in agreement with [ 35 S]PTU studies, no direct correlation was found between thyroid uptake or oxidation of [ 35 S]MMI and thyroidal total iodine, the accumulation or organification of acute [ 125 I]iodide, the occurrence of the Wolff-Chaikoff effect or saturation of thyroid iodide transport.