vasoactive-intestinal-peptide and Graves-Disease

Topics: Antibodies, Monoclonal; Biomarkers; Biomarkers, Tumor; Carcinoid Tumor; Female; Graves Disease; Humans; Male; Neuroendocrine Tumors; Octreotide; Radionuclide Imaging; Receptors, Somatostatin; Sensitivity and Specificity; Vasoactive Intestinal Peptide

Vasoactive intestinal peptide (VIP) is a neuropeptide with potent immunoregulatory properties. Reduced serum VIP levels and alterations in VIP receptors/signaling on immune cells have been associated with different inflammatory/autoimmune diseases. However, its role in autoimmune thyroid diseases (AITD) remains unknown. This study examined the interrelationship between VIP system, autoimmune background and thyroid hormones in peripheral immune cells in patients with AITD. Only Graves' disease (GD) patients showed significantly lower serum VIP levels when compared to healthy subjects and to Hashimoto's thyroiditis patients. Serum VIP levels were lower at the onset of GD, showing a significant negative correlation with thyroid hormone levels. The expression of VIP receptors, VPAC1 and VPAC2, was significantly upregulated in peripheral blood mononuclear cells (PBMC) from GD patients. There was an impairment of VIP signalling in these patients, probably attributable to a dysfunction of VPAC1 with preservation of VPAC2. The correlation between VPAC1 and thyroid hormone receptor expression in PBMC from healthy subjects was lost in GD patients. In summary, the VIP system is altered in peripheral immune cells of GD patients and this finding is associated with different thyroid hormone receptor patterns, showing a dynamic inter-regulation and a prominent role of VIP in this setting.

Topics: Adult; Female; Graves Disease; Humans; Male; Middle Aged; Receptors, Vasoactive Intestinal Peptide, Type II; Receptors, Vasoactive Intestinal Polypeptide, Type I; Thyroid Hormones; Vasoactive Intestinal Peptide

As the interactions of iodothyronines on adrenergic and vipergic receptors are not clear, the effect of exogenous T3 and T4 on catecholamine- and VIP-induced cAMP accumulation in human normal thyroid cells after eight days of primary culture has been investigated. To evaluate the effect of endogenous iodothyronines, the response of the adenylate cyclase system to isoprenaline, adrenaline, VIP, and TSH was studied during a 10 d period. T3 and T4 were unable to modify the catecholamine- and VIP-induced cAMP accumulation in human normal thyroid cells after 6-8 days of culture, while the response to TSH was significantly inhibited. In cells cultured from thyrotoxic tissue, the response of the adenylate cyclase system to catecholamines and VIP, during a 10 d primary culture, showed a behaviour similar to controls. TSH responsiveness was negligible up to the fourth day of culture, while in normal cells a response to all the agonists was present from the beginning. In view of the lack of effect of iodothyronines on catecholamine- and VIP-induced cAMP accumulation, and of the superimposable behaviour of the response to catecholamines and VIP in normal and hyperthyroid cells during the first days of culture, we can conclude that iodothyronines do not directly modify the response of the adenylate cyclase system to adrenergic and vipergic stimulation in human thyroid follicular cells. The lack of responsiveness to TSH of cells obtained from hyperthyroid tissue during the first 4 d of culture, associated with normal responsiveness to catecholamines and VIP, points to a possible involvement of biogenic amines and neuropeptides in sustaining such hyperthyroid states.

Topics: Adult; Catecholamines; Cells, Cultured; Cyclic AMP; Female; Graves Disease; Humans; Male; Middle Aged; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine; Vasoactive Intestinal Peptide