Regulation of Cyclic Nucleotide and Prostaglandin Formation in Normal Human Thyroid Tissue and in Autonomous Nodules*

Publisher Website
Google Scholar
Abstract
We have investigated the regulation of the human thyroid 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 β-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 F2α release. These effects were mimicked by ionophore A23187 and abolished in a calciumdeprived 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 controlshave 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 lesssensitive to acetylcholine (cGMP accumulation) and more sensitive to norepinephrine (cAMP accumulation).

This publication has 0 references indexed in Scilit: