Thyrocyte release of asymmetric dimethylarginine does not account for human thyrocyte inhibition of endothelial cell cyclic GMP

Abstract

Background: The thyroid gland produces and responds to the signalling molecule nitric oxide (NO). The activity of NO synthase (NOS) may be regulated by endogenous NOS inhibitors such as asymmetric dimethylarginine (ADMA). Objective: To investigate whether human thyrocytes are capable of regulating NOS activity via the production of ADMA. Design: Human thyrocytes were incubated with human umbilical vein endothelial cells (HUVEC) in order to determine the effect on HUVEC NOS activity. HUVEC cGMP production over a 3-h period was measured as an indicator of NOS activity in the absence and presence of thyrocytes. To determine thyrocyte production of ADMA, samples of conditioned media were analysed by HPLC. Results: The presence of primary human thyrocytes or immortalized human thyrocyte SGHTL-189 cells caused a significant inhibition of both basal (approximately 57% inhibition) and thrombinstimulated (approximately 42% inhibition) HUVEC cGMP production. Both primary human thyrocytes and SGHTL-189 cells released ADMA (approximately 0.28 mg per 10 6 thyrocytes over a 3-day period). However, excess L-arginine, the natural substrate for NOS, was unable to overcome thyrocyte inhibition of HUVEC cGMP production. Conclusion: These data indicate that human thyrocytes potently reduce endothelial cell cGMP concentrations, and that thyrocytes produce the endogenous NOS inhibitor, ADMA. However, the inhibition of endothelial cGMP is not mediated via thyrocyte production of a competitive NOS inhibitor.

Urinary metabolomics reveals glycemic and coffee associated signatures of thyroid function in two population-based cohorts

“…These results were confirmed in patients with Graves' disease [ 47 ] or hyperthyroidism [ 48 , 49 ] and therefore fit in with our longitudinal findings of a higher decrease in FT4 levels among subjects with low DMA. Furthermore, experimental studies confirmed a relationship between ADMA and thyroid function by showing a down-regulation of the DDAH1 gene in mice liver following T3 treatment [ 50 ] as well as the production of endogenous ADMA in primary human thyrocytes [ 51 ]. Beside ADMA the consumption of fish and seafood represent one source of DMA and therefore DMA might be marker of the dietary intake of iodine.…”

Contractile responses of human thyroid arteries to vasopressin

“…NO synthase, the enzyme responsible for the formation of NO (Palmer et al, 1988) is present in the thyroid follicular cells and in endothelial cells of the human thyroid gland (Colin et al, 1997), and human thyrocites produce the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) (Colin et al, 1995;Millatt et al, 2000). In addition, NO modulates the response of human thyroid arteries to acetylcholine and noradrenaline (Torondel et al, 2004).…”

Relationships between serum levels of thyroid hormones and serum concentrations of asymmetric dimethylarginine (ADMA) and N-terminal-pro-B-type natriuretic peptide (NT-proBNP) in patients with Graves’ disease

“…The possible mechanism for this observation was not investigated in this study. It was demonstrated that endothelial isoform of NO synthase was abundantly expressed in human thyroid gland, especially in thyroid tissues from hyperthyroid patients [25], and human thyrocytes could really release ADMA [26]. Since the thyroid blood flow in hyperthyroid patients is significantly increased, the overproduction of ADMA in hyperthyroidism might also be a compensatory mechanism to reduce NO production and peripheral vasodilatation [18].…”