Heterogeneous signal pathways through TSH receptors in porcine thyroid cells following stimulation with Graves' immunoglobulin G

Abstract

Objective: We compared different signal transduction pathways through thyroid stimulating hormone receptor (TSH-R) in porcine thyroid cells (PTC) following stimulation with thyroid stimulating hormone (TSH) and 11 thyroid stimulating immunoglobulin samples (TSI) obtained from patients with Graves' disease. Design: Following stimulation with TSI, the level of inositol trisphosphate (IP 3 ) and [Ca 2þ ] i , as well as the membrane bound protein kinase C (PKC) activity and the intensity of the arachidonic acid (AA) cascade, were determined in PTC.Results: Seven out of eleven TSI samples activated PTC through IP 3 generation, elevated [Ca 2þ ] i from the intracellular pools, exhibited verapamil-insensitive membrane-bound PKC activation, and enhanced release of [ 14 C]AA derivates (however, one of the samples was also able to take up Ca 2þ from the extracellular space). Four out of eleven TSI samples did not activate the phospholipase C (PLC) system in which case the Ca 2þ signal occurred only in the presence of extracellular Ca 2þ , the membrane bound PKC activation was verapamil sensitive, and in two of these four TSI samples, the AA release was extremely high. Conclusions:The simultaneous examination of the majority of the known signal pathways using TSI samples showed that TSI samples from different patients activate thyroid cells through different pathways. Their effects differ from that of TSH and, to a certain extent, from each other. The results give a certain new insight into the intracellular mechanisms exerted by TSI.

Thyroxine therapy ameliorates serum levels of eicosanoids in Chinese subclinical hypothyroidism patients

“…However, studies of the effects of TSH on phospholipid metabolism are still relatively scarce. It has been reported that TSH attenuates prostacyclin (PGI2) levels, resulting in endothelial dysfunction and promoting the release of AA by activating PLA2 by IP3 or Ca 2+ [27,28] . Our study indicated that the elevated TSH levels in SH patients were closely related to abnormal levels of many bioactive eicosanoids produced from AA metabolism.…”

Thyroid Hormone and Thyrotropin Regulate Intracellular Free Calcium Concentrations in Human Polymorphonuclear Leukocytes: In Vivo and in vitro Studies

“…Circumstantial evidence in patients with thyroid disorders supports the possibility of a relationship between thyroid status and PMN function: indeed, hyperthyroidism has been associated with a reduced number of circulating PMNs, increased index of spontaneous nitroblue tetrazolium reduction, decreased phagocytosis index and lisozyme activity (8), and increased opsonized zymosan-stimulated O 2 -consumption (9). On the other hand, PMNs from patients with .severe hypothyroidism may have reduced bactericidal capacity (l0) or oxidative metabolism (11).…”