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).
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000236:Adenoma / Q000378:metabolism*; D000328:Adult; D001285:Atropine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D005260:Female; D005459:Fluorides / Q000494:pharmacology; D006801:Humans; D008875:Middle Aged; D010830:Physostigmine / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D011458:Prostaglandins E / Q000494:pharmacology; D013961:Thyroid Gland / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology
D011453:Prostaglandins; D011458:Prostaglandins E; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D000001:Calcimycin; D001285:Atropine; D002217:Carbachol; D013972:Thyrotropin; D002772:Cholera Toxin; D010830:Physostigmine; D000242:Cyclic AMP; D006152:Cyclic GMP; D000109:Acetylcholine; D005459:Fluorides