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

Abstract

Intracellular free calcium concentrations ([Ca++li) were studied in polymorphonuclear leukocytes (PMNs) from 13 athyreotic patients who had been previously treated by total thyroidectomy and radioiodine therapy for differentiated thyroid carcinoma, and from age-and sex-matched euthyroid healthy controls. Patients were studied twice, when hypothyroid (visit 1) and after restoration of euthyroidism by L-T 4 TSH-suppressive therapy (visit 2). PMNs from patients at visit 1 had significantly lower resting lCa++). levels compared to both visit 2 and controls. Values at visit 2 did not differ from those of the controls. Stimulus-induced [Ca"], rise was also significantly blunted at visit 1 -and normalized at visit 2, possibly through a differential contribution of distinct intracellular Ca" stores, as suggested by the response pattern to the chemotactic agent, N-formyl-Met-Leu-Phe (fMLP), to the selective SERCA pump inhibitor, thapsigargine, and to the mitochondrial uncoupler, carbonyl cyanide p-trifluoromethoxyphenyl-hydrazone (FCCP). In vitro treatment of PMNs from healthy subjects with high TSH concentrations impaired intracellular Ca" store function. Both resting [Ca"], levels and fMLP-induced [Ca"], rise increased in the presence either of low-concentration TSH or of T 4 , but effects of TSH and T 4 were not additive. T J , rT J , and TRIAC had no effect. In conclusion, this study provides evidence for a direct relationship between thyroid status and [Ca"], homeostasis in human PMNs, mainly related to direct actions of TSH and T 4 on these cells.Human leukocytes express both nuclear receptors for triiodothyronine (T3) and plasma membrane receptors for thyroid-stimulating hormone (TSH; 1-3), but effects of thyroid hormones and TSH on these cells are poorly documented at present. In particular, available data

Serum Concentrations of Estradiol and Free T4 Are Inversely Correlated With Sperm DNA Damage in Men From an Infertility Clinic

“…In summary, we found statistically significant associations between serum levels of several hormones and sperm DNA damage, most notably protective associations involving estradiol and free T 4 . Estradiol and thyroid hormone play a role in calcium metabolism (Khosla et al, 1998; Lindblom et al, 2001; Kumar and Prasad, 2003) and may prevent elevated intracellular concentrations of calcium (Hilton et al, 2006; Marino et al, 2006) and subsequent DNA damage (Ray et al, 1993; Liu and Huang, 1996; Bentle et al, 2006). However, at this time it is not known whether hormones are in the causal pathway for sperm DNA damage or if both decreased hormone (estradiol, free T 4 ) levels and increased sperm DNA damage are related to another unmeasured factor that is a common cause of both.…”

Thyrotropin aggravates atherosclerosis by promoting macrophage inflammation in plaques

“…It should be noted that although our results obtained from TSHR MKO mice highlighted macrophages as critical targets of the atherogenic effect of TSH, LyzCRE-mediated deletion can also affects myeloid cells other than macrophages, such as monocytes and neutrophils, which might have confounded the end points. However, the effect of TSH on monocytes or neutrophils may not play an important role in atherosclerosis, given that TSH does not activate neutrophils (Kiss et al, 1997; Marino et al, 2006; Fig. S5 C) or promote monocyte recruitment by acting on monocytes directly (Fig.…”

Effect of Acute Caffeine Exposure on Blood Glucose and Hepatic Glycogen Content in Normal and Thyroidectomized Male Wistar Rats

“…The increased adrenaline mediates increase blood glucose by promoting hepatic glycogenolysis and gluconeogenesis while it inhibits insulin-dependent glucose disposal (Sherwin and Saccà, 1984). Several studies have documented that intracellular calcium mobilization is dependent on thyroid hormone (Dho et al, 1989;Marino et al, 2006) and thyroidectomy had been shown to suppress intracellular calcium release (Amadi et al, 2005), it conceivable that caffeine-mediated calcium release which is associated with increased adrenaline release will be hindered in the thyroidectomized rats, it is therefore not surprising that caffeine-elicited increase blood glucose was reduced from 210 % to 180 % in the thyroidectomized rats of this study. The lack of total abolishment of the caffeine-induced increased blood glucose in the thyroidectomized rats of the current study may be linked with the interaction of caffeine with adenosine receptor, caffeine is a potent non-selective adenosine receptor antagonist and exerts most of its biological activities by blocking all types of adenosine receptors (Ribeiro and Sebastião, 2010).…”