Role of thyroglobulin endocytic pathways in the control of thyroid hormone release

2000 ◽  
Vol 279 (5) ◽  
pp. C1295-C1306 ◽  
Author(s):  
Michele Marinò ◽  
Robert T. McCluskey

Thyroglobulin (Tg), the thyroid hormone precursor, is synthesized by thyrocytes and secreted into the colloid. Hormone release requires uptake of Tg by thyrocytes and degradation in lysosomes. This process must be precisely regulated. Tg uptake occurs mainly by micropinocytosis, which can result from both fluid-phase pinocytosis and receptor-mediated endocytosis. Because Tg is highly concentrated in the colloid, fluid-phase pinocytosis or low-affinity receptors should provide sufficient Tg uptake for hormone release; high-affinity receptors may serve to target Tg away from lysosomes, through recycling into the colloid or by transcytosis into the bloodstream. Several apical receptors have been suggested to play roles in Tg uptake and intracellular trafficking. A thyroid asialoglycoprotein receptor may internalize and recycle immature forms of Tg back to the colloid, a function also attributed to an as yet unidentified N-acetylglucosamine receptor. Megalin mediates Tg uptake by thyrocytes, especially under intense thyroid-stimulating hormone stimulation, resulting in transcytosis of Tg from the colloid to the bloodstream, a function that prevents excessive hormone release.

1999 ◽  
Vol 276 (2) ◽  
pp. R357-R362 ◽  
Author(s):  
Tom van der Poll ◽  
Erik Endert ◽  
Susette M. Coyle ◽  
Jan M. Agosti ◽  
Stephen F. Lowry

To determine the role of tumor necrosis factor (TNF) in endotoxin-induced changes in plasma thyroid hormone and thyroid-stimulating hormone (TSH) concentrations, 24 healthy postabsorptive humans were studied on a control study day ( n= 6), after infusion of a recombinant TNF receptor IgG fusion protein (TNFR:Fc; 6 mg/m2; n = 6) after intravenous injection of endotoxin (2 ng/kg; n = 6), or after administration of endotoxin with TNFR:Fc ( n = 6). Administration of TNFR:Fc alone did not affect thyroid hormone or TSH levels when compared with the control day. Endotoxin induced a transient rise in plasma TNF activity (1.5 h: 219 ± 42 pg/ml), which was completely prevented by TNFR:Fc ( P < 0.05). After endotoxin administration, plasmal-thyroxine (T4), free T4, 3,5,3′-triiodothyronine (T3), and TSH were lower and 3,3′,5′-triiodothyronine was higher than on the control day (all P < 0.05). Coinfusion of TNFR:Fc with endotoxin did not influence these endotoxin-induced changes. Our results suggest that endogenous TNF does not play an important role in the alterations in plasma thyroid hormone and TSH concentrations induced by mild endotoxemia in healthy humans.


1961 ◽  
Vol 201 (6) ◽  
pp. 1049-1052 ◽  
Author(s):  
M. Jay Goodkind ◽  
David H. Fram ◽  
Michael Roberts

Normal and thyroidectomized guinea pigs were subjected to treatment with either triiodothyronine or thyroid-stimulating hormone. Determinations of myocardial catecholamine content and serum protein-bound iodine revealed a significant increase in myocardial norepinephrine content in the markedly thyrotoxic animal, and a significant decrease in norepinephrine content of the myocardium of hypothyroid animals. The significance of these findings in defining the role of catecholamines in various states of thyroid function is discussed.


2016 ◽  
Vol 175 (6) ◽  
pp. R255-R263 ◽  
Author(s):  
Kerry J Welsh ◽  
Steven J Soldin

Hypothyroidism is a very common disorder worldwide, for which the usual treatment is monotherapy with levothyroxine (L-T4). However, a number of patients treated with L-T4 continue to report symptoms of hypothyroidism despite seemingly normal levels of thyroid-stimulating hormone (TSH), free-T3 (FT3) and free-T4 (FT4) measured by immunoassay. This review summarizes the limitations of the immunoassays commonly used to measure thyroid hormone levels and emphasizes the advantages of the role of liquid chromatography-tandem mass spectrometry (LC-MS/MS). Immunoassays for free thyroid hormone are affected by alterations in serum binding proteins that occur in many physiological and disease states. Multiple studies show falsely normal values for T3, FT3 and FT4 by immunoassay that are below the reference interval when measured by (ultrafiltration) LC-MS/MS, a reference method. We suggest evaluation of thyroid hormone levels by ultrafiltration LC-MS/MS for patients who continue to experience hypothyroid symptoms on LT-4. This may help identify the approximately 20% subset of patients who would benefit from addition of T3 to their treatment regimen (combination therapy).


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