Inhibition by Iodide of the Activation of the Thyroid Cyclic 3′,5′-AMP System

Abstract

The action of iodide on the cyclic AMP system of dog thyroid slices has been studied. Iodide inhibits the enhancement of cyclic AMP accumulation in the presence of TSH. Such an effect is also observed in horse, beef and sheep thyroid slices, but not in dog kidney slices stimulated by parathyroid hormone or in rat parotid slices stimulated by isoproterenol. The effect in dog thyroid slices is suppressed by 1mM NaClO4, 1mM methimazole and 1mM propylthiouracil. Similar data have been obtained for prostaglandin E1 stimulation. Effects of thyrotropin mediated by cyclic AMP, i.e., activation of iodothyronine secretion, 1-14C-glucose oxidation, and lactate formation, were also inhibited by iodide but not by iodide and methimazole. Similar activations when caused by dbcAMP were not inhibited by iodide. The data suggest a model in which an intracellular agent resulting from the oxidation of iodide acts on the thyroid cyclic AMP system.

Upregulation of the angiogenic factors PlGF, VEGF and their receptors (Flt-1, Flk-1/KDR) by TSH in cultured thyrocytes and in the thyroid gland of thiouracil-fed rats suggest a TSH-dependent paracrine mechanism for goiter hypervascularization

“…The increase in VEGF mRNA levels occurred very early (Figure 7a, middle panel), with a peak after 30 ± 60 min, whereas PlGF transcript levels started to increase slowly and peaked at 3 ± 6 h from the beginning of the treatment ( Figure 7a, upper panel), suggesting that dierent molecular mechanisms may regulate the mRNA expression of VEGF and PlGF. TSH modulates thyroid functions by binding to the high anity receptor (TSHR) on the thyrocyte surface; receptor activation triggers the cAMP-dependent protein kinase pathway (PKA) (Rognoni et al, 1984;Yun et al, 1986;Van Sande et al, 1975). In agreement with the results obtained with TSH, the mRNA expression of VEGF and PlGF was increased in thyroid cells also by treatment with forskolin, at a concentration of 25 mM (data not shown).…”

“…TSH-induced upregulation of VEGF mRNA occurs as early as 30 min and does not require protein synthesis whereas PlGF expression occurs later and appears to require, in part, protein synthesis. Since TSH modulates cAMP-dependent gene expression by binding to its high-anity TSHR on the thyrocyte cell surface and activating downstream the cAMP-dependent PKA pathway (Yun et al, 1986;Van Sande et al, 1975;Dumont et al, 1992), we also investigated whether the activation of the PKA-dependent pathway by forskolin exerted some eect on the mRNA expression of PlGF and VEGF. Accordingly, forskolin-stimulated increase in the intracellular cAMP level induced a dose-and time-dependent increase in the VEGF and PlGF mRNA expression, suggesting that the action of TSH on the VEGF and PlGF mRNA level is mediated through the PKA-dependent pathway.…”

Inhibition of intrathyroidal dehalogenation by iodide

“…Paradoxically, for this inhibition to occur, it is mandatory that iodide uptake and/or organification remain intact; i.e. when TPO is pharmacologically blocked before iodide administration, the Wolff-Chaikoff effect does not occur (van Sande et al 1975). To explain this paradox, the participation of an unknown inhibitory iodinated compound has been suggested, possibly a lipid derivative like iodolactone or iodohexadecanal (Dugrillon et al 1990, Panneels et al 1996.…”

Pairs of cyclic AMP analogs, that are specifically synergistic for type I and type II cAMP‐dependent protein kinases, mimic thyrotropin effects on the function, differentiation expression and mitogenesis of dog thyroid cells

“…Indeed, 1 mU/ml is an optimal concentration of thyrotropin for secretion, but iodination is maximally stimulated between 10 mU/ml and 30 mU/ml thyrotropin [36]. Previous studies showing that forskolin [53], cholera toxin [50], N6,2'-O-dibutyryladenosine 3',5'-phosphate (Bt2cAMP) [51] and adenosine 3',5'-monophosphorothioate (cAMP[S]) [52] stimulated iodide uptake by dog thyroid led us to expect that our series of cAMP analogs would have the same effect. This was indeed observed, although the analogs were, in general, less potent than thyrotropin.…”