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Biomedical subjects

J Mockel

Publications and source records attributed to J Mockel.

At least 73 records · Page 4Linked to original sources
PubMed1980

In vitro regulation of ornithine decarboxylase in dog thyroid slices.

Ornithine decarboxylase (ODC) activity in dog thyroid slices incubated in vitro disappears when protein or RNA synthesis is inhibited. Thus, as in other tissues, the level of the enzyme reflects a balance between rapid synthesis and catabolism. TSH, dibutyryl cAMP, prostaglandin E1 (PGE1), and cholera toxin all stimulated dog thyroid ODC activity. These actions were potentiated by the inhibitor of phosphodiesterases, 4-(3-butoxy-4-methoxy-benzyl)2-imidazolidinone (Ro 20-1724), and reproduced by high concentrations of this inhibitor, while 1-methyl-3-isobutylxanthine inhibited ODC induction. Iodide blocked the action of TSH; this inhibition was relieved by methimazole. Calcium depletion or manganese addition depressed enzyme levels in control and stimulated tissue. In some cases (ionophore A23187 addition and calcium depletion), total protein synthesis was also depressed. Carbamylcholine and the ionophore A23187, which can raise cGMP in thyroid slices, inhibited TSH and dibutyryl cAMP induced ODC increases, PGF1 alpha was inhibitory to ODC stimulation. Indomethacin, which had no effect on TSH action, relieved carbamylcholine inhibition. These results show that dog thyroid ODC is stimulated by TSH through cAMP, and suggest that cholinergic stimulation of the tissue blocks TSH activation of the enzyme, possibly at a step beyond cAMP synthesis, by increasing PGF synthesis. The effect of carbamylcholine is not due to cGMP, since it can be obtained under conditions where basal cGMP levels are not increased.

1-Methyl-3-isobutylxanthine↗
PubMed1980

Regulation of cyclic nucleotide and prostaglandin formation in normal human thyroid tissue and in autonomous nodules.

We have investigated the regulation of the human throid gland based on controls discovered in the dog thyroid gland. TSH and thyroid-stimulating immunoglobulin enhanced cAMP accumulation, which supports the validity of the Sutherland model for the action of TSH on the human thyroid. Iodide inhibited TSH- and thyroid-stimulating immunoglobulin-activated cAMP accumulation and this effect was reduced by methimazole, showing that, in this tissue, iodide, through an oxidized derivative, depresses the TSH-cAMP system. Contrary to the hypothesis of a short feedback loop of thyroid hormone, no thyroid effect of T3 or T4 was found. Adrenergic agents (norepinephrine and isoproterenol) enhanced cAMP accumulation; this effect was inhibited by dl-propranolol but not by d-propranolol or phentolamine. This suggests a positive control of the thyroid cAMP system by beta-adrenergic receptors. Histamine also increased cAMP accumulation. However, the role of these controls is unknown. Acetylcholine, by a muscarinic type effect, enhanced cGMP accumulation and prostaglandin E2 and prostaglandin F2 alpha release. These effects were mimicked by ionophore A23187 and abolished in a calcium-deprived medium, which suggests that they are secondary to a raised Ca++ influx. The results are summarized in a general working model of human thyroid regulation. These biochemical controls have been compared in normal tissue and autonomous nodules. No evidence of increased sensitivity to TSH of the nodular tissue was found. On the other hand, this tissue was less sensitive to acetylcholine (cGMP accumulation) and more sensitive to norepinephrine (cAMP accumulation).

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1980

Thyroglobulin and thyroid hormone release after intravenous administration of bovine thyrotropin in man.

To elucidate the mechanism of thyroglobulin (Tg) release in man, the effects of an iv injection of a submaximal dose of bovine TSH (bTSH) on the serum levels of Tg were compared with the effects on serum T3 and T4. After the administration of bTSH, short term kinetics (0-4 h) were studied in eight subjects receiving 0.5 IU bTSH and seven subjects receiving 1 IU bTSH. Serum Tg did not significantly increase in either of the short term studies. By contrast, serum T3 increased significantly and linearly after the administration of 0.5 and 1 IU bTSH; serum T4 also rose but only after 1 IU bTSH. Long term kinetics (0-120 h) were studied in seven additional subjects after the iv administration of 1 IU bTSH; serum bTSH was no longer detectable after 8 h. Maximum serum concentrations of T3 were obtained at about 4 h, maximum serum concentrations of T4 were obtained between 4-8 h. Serum Tg levels increased linearly with time during the first 24 h. Maximum serum Tg levels correlated well with basal serum Tg values (r = 0.97; P < 0.001). The maximal increment in Tg correlated inversely with the maximal increment in T3 (r = 0.71; P < 0.05). The half-life of Tg was estimated to be approximately 4 days by measuring the disappearance rate of Tg after its peak level was attained.

Adult↗
PubMed1978

Kinetics of dog thyroid secretion in vitro.

The time sequence of radioiodine sequestration and secretion (BE131I) have been compared in dog thyroid slices prelabeled with 131I in vivo and incubated in vitro with or without TSH. Sequestration has been taken to be the amount of radioiodine present in phagocytic vacuoles or colloid droplets; the TSH or (Bu)2cAMP stimulation of the basal values was suppressed by endocytosis blocking drugs. TSH induced a sequestrated radioactivity (S) after 5 min and a stimulated secretion after 20 min. The secretion rate was constant: 1%/h (mean +/- SD = 1.0 +/- 0.4; n = 7) of the total radioactivity of the slices. At equilibrium, S was constant and equal to less than 1% of the total radioactivity. The half-life of S, assuming a disappearance rate proportional to S, was 26 min (26 +/- 4; n = 5); assuming a disappearance rate independent of S, the lifetime was 44 min (44 +/- 7; n = 6). At the steady state, the limiting step of maximally stimulated secretion was the hydrolysis of the sequestrated radioactivity and endocytosis rate was equal to secretion rate. Without TSH, a constant BEI release (0.23% +/- 0.07%/h; n = 7), insensitive to cytochalasin B, was observed, which corresponded to basal secretion.

Animals↗
PubMed1978

[Calcium, cGMP and cAMP roles in thyroid regulation (author's transl)].

Cholinergic agents induce an accumulation of cGMP in thyroid tissue and inhibit cAMP accumulation and thyroid hormone secretion resulting from TSH action. The aim of the present work was to determine the respective roles of Ca++ and/or cGMP in these actions. The results show that two complementary mechanisms may be demonstrated: 1) cGMP activates phosphodiesterase activity and cAMP hydrolysis. 2) Independently of cyclic nucleotide concentrations, increased intracytoplasmic Ca++ directly inhibits TSH induced stimulated hormone secretion.

Animals↗