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Abstract.

In an attempt to study intrinsic regulatory mechanism involved in iodine metabolism, chronic and acute effects of TSH, PGE₂ and DBC on iodine uptake, iodide discharge and organic binding of iodine were examined using cultured porcine thyroid cells.

Culture in the presence of TSH, PGE₂ and DBC for 6 days maintained the ability of thyroid cells to take up iodide and organify it, but culture in the absence of these substances failed to do so. When incubated with Nal in the presence of 1 mm methylmercaptoimidazole (MMI), the cells took up iodide and this accumulated iodide was discharged by TSH, PGE₂ and DBC. TSH-, PGE₂- and DBC-stimulated iodide discharge was depressed greatly after chronic exposure to TSH, PGE₂ or DBC. This refractoriness of TSH-, PGE₂- or DBC-stimulated iodide dishcarge was not specific for each thyroid stimulating substance; previous exposure to TSH, PGE₂ or DBC induced refractoriness of TSH-, PGE₂- and DBC-stimulated iodide discharge, providing evidence for the existence of refractoriness at the level of cyclic AMP action on iodide discharge. When incubated with Nal in the absence of MMI, the cells took up iodide and organified it. After 30 min incubation with Nal, TSH, PGE₂ and DBC were added and they stimulated iodide organification further. This TSH-, and PGE₂-stimulated iodide organification was also depressed after exposure to TSH or PGE₂.

These data indicate that, as an intrinsic regulatory mechanism, refractoriness is operating at the level of cAMP action on iodine discharge and organification.

Abstract.

Adipocytes from streptozotocin-diabetic rats showed a markedly reduced lipolytic response to glucagon concomitant with a 90% or greater decrease in the number of glucagon receptors per cell. In contrast, β-adrenergic receptors assessed by [³H]dihydroalprenolol binding and lipolysis stimulated by isoproterenol, dibutyryl 3′5′-cyclic AMP and 3-isobutyl-1-methylxanthine were reduced by only 10–25% in diabetic rats compared with controls. Furthermore, quantitative analysis of the relationship between the amount of cell-bound glucagon and the hormone-stimulated lipolysis revealed that the function of the remaining 10% of glucagon receptors remained intact in cells from diabetic animals. These findings suggest that the lipolytic cascades, including β-adrenergic receptors, in adipocytes are not greatly impaired by diabetes, and therefore, the unresponsiveness of these cells to glucagon is mostly due to a marked reduction in the number of glucagon receptors, probably as a result of a down-regulation by postprandial hyperglucagonemia.

Abstract. A 46-year-old woman had signs of thyrotoxicosis and galactorrhoea. Serum immunoreactive TSH and its α-subunit increased in the presence of high serum triiodothyronine (T₃), thyroxine (T₄), and free T₄ concentrations, whereas β-subunit TSH was undetectable. Exogenous TRH failed to increase serum TSH. Serum TSH was markedly suppressed by glucocorticoid, but was increased by antithyroid drug. l-Dopa or bromocriptine partially suppressed, but nomifensine had no influence on serum TSH.

Serum prolactin (Prl) was above normal and markedly increased by TRH, but depressed by bromocriptine and not suppressed by nomifensine. Plasma TRH was normal in the hyperthyroid state, but was increased by glucocorticoid and antithyroid drug. Excess thyroid hormone depressed plasma TRH concentrations. Basal serum GH levels were constantly low. Transsphenoidal removal of the tumour normalized serum hormones (T₃, T₄ free T₄, TSH, α-subunit and Prl), and eradicated the clinical signs of hyperthyroidism and galactorrhoea. Histological study of the tumour tissue demonstrated both thyrotrophes and somatotrophes. A reciprocal relationship between serum TSH and T₄ concentrations shifted to a higher level before but was normalized after removal of the tumour. Ten months later, the clinical signs of thyrotoxicosis and the increase in serum thyroid hormone recurred without a concomitant increase in serum TSH and its α-subunit. Thyroidal auto-antibodies were slightly positive, but thyrotrophin-binding inhibitor immunoglobulin (TBII) was negative. Administration of antithyroid drug produced a euthyroid state, but 3 years later, discontinuation of the treatment resulted in recurrent hyperthyroidism without suppressed plasma TRH and with no evidence of regrowth of the pituitary tumour.

It is suggested that the patient initially had hyperthyroidism owing to excessive TSH secretion from the tumour caused by abnormal TRH secretion, and subsequently had hyperthyroidism owing to Graves' disease.