Regulatory Networks in the Acute Control of Thyroid Function
Two main regulatory pathways are involved in the acute control of dog thyroid cell function: TSH activates thyroid adenylate cyclase and, through cyclic AMP, stimulates both thyroid hormone synthesis and secretion. TSI, E prostaglandins, and norepinephrine, through β receptors, all act similarly. Norepinephrine, through α receptors and the inhibitory pathway of cyclase (NI), directly inhibits adenylate cyclase and the cyclic AMP-mediated effects (Fig. 1). Acetylcholine, through muscarinic receptors, enhances calcium influx and phosphatidylinositol (PI) turnover. The latter process releases in the cell two other intracellular signal molecules, diacylglycerol (DAG) and myoinositol 1,4,5-phosphate (IP3). IP3 induces the intracellular release of Ca++, while DAG activates protein kinase C (Fig. 2). Increased cytosolic calcium enhances H2O2 generation and iodination, cyclic GMP accumulation, and arachidonate release; it activates calmodulin-dependent cyclic nucleotide phosphodiesterase and, thus, lowers cyclic AMP levels and thyroid hormone secretion (Fig. 1). These effects are mimicked by high extracellular calcium and ionophore A23187.
KeywordsPhorbol Ester Thyroid Hormone Synthesis Inhibit Adenylate Cyclase Intracellular Signal Molecule Thyroid Hormone Secretion
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