NICOLA JUAN PABLO
Congresos y reuniones científicas
Título:
Role of 2-iodohexadecanal in the thyroid autoregulatory mechanism
Autor/es:
ROSSICH, LE; THOMASZ, L; NICOLA, JP; OGLIO, ; MASINI-REPISO, AM; PISAREV, M; JUVENAL, GJ
Lugar:
Paris
Reunión:
Congreso; XIV Congreso Internacional de Tiroides; 2010
Institución organizadora:
International thyroid association
Resumen:
Background: Although thyroid gland function is mainly under the control of pituitary TSH, other factors may also play a role in this process. Iodine is not used only by the thyroid to synthesize thyroid hormones but also directly influences a number of thyroid parameters such as thyroid proliferation and function. Iodine must be organified in order to
exert its effect. The nature of this/these iodocompound/s is still unknown. Several iodinated lipids are biosynthesized by the thyroid and they were postulated as intermediaries in the action of iodide. Among them 6 iodo-d- lactone (IL-δ) and 2-iodohexadecanal (IHD) have been identified and data from different laboratories have shown that these iodolipids inhibit
several thyroid parameters and it has proposed that they could play a role in thyroid autoregulation.
The aim of this study was to compare the effect of iodide and IHD on several thyroid parameters.
Methods and Results: FRTL-5 cells were incubated with the different compounds during one day. IHD inhibited iodide uptake induced by TSH in a concentration-dependent manner, (TSH = 660.59; IHD 30 μM = 292.17*; IHD 6 μM = 436.58*; IHD 1 μM = 502.35; KI 30 μM = 396.18*; KI 6 μM = 534.44*; KI 1 μM = 625.39 n.s., without TSH =184.85, values are expressed as cpm/ μg protein * = p<0.001). IHD at concentrations of 30 μM, 6 μM and 1 μM reduced iodide uptake by 77 %, 47 % and 33 % respectively. Under similar conditions KI caused the following inhibition: 66 % at 30 μM, 27 % at 6 μM; while at 1 μM the inhibition was not significant Western Blots were done for NIS and Tg. Treatment with IHD diminished Tg and NIS levels. Tg (TSH = 100 %, IHD 30 μM= 40 %, IHD 6 μM= 57 %, p<0.001); and NIS (TSH = 100 %, IHD 30 μM= 74%, IHD 6μM= 88 %, <0.001).
To further explore the molecular mechanism involved in IHD action, several mRNA level for thyroid specific proteins (TSP) were measured by semiquantitative RT-PCR. Table 1 shows that the pre-treatment of FRTL-5 cells with KI caused a significant reduction on TSP mRNA levels. This inhibition was relieved in some cases by MMI (10-3M) demonstrating
that an organic iodocompound is required in this action. When the cells were treated with IHD, an inhibition of TSP mRNA were also observed. While IHD exerts its effect in the presence of MMI indicating that its effect is independent of the iodide which could be released from its dehalogenation, the effect of the halogen is reversed in some cases by the
presence of the antithyroid drug, showing that iodide must be organified in order to exert its effect.
Conclusion: These findings indicate that IHD reproduces the effects of excess iodide and support its role in the autoregulatory mechanism.
exert its effect. The nature of this/these iodocompound/s is still unknown. Several iodinated lipids are biosynthesized by the thyroid and they were postulated as intermediaries in the action of iodide. Among them 6 iodo-d- lactone (IL-δ) and 2-iodohexadecanal (IHD) have been identified and data from different laboratories have shown that these iodolipids inhibit
several thyroid parameters and it has proposed that they could play a role in thyroid autoregulation.
The aim of this study was to compare the effect of iodide and IHD on several thyroid parameters.
Methods and Results: FRTL-5 cells were incubated with the different compounds during one day. IHD inhibited iodide uptake induced by TSH in a concentration-dependent manner, (TSH = 660.59; IHD 30 μM = 292.17*; IHD 6 μM = 436.58*; IHD 1 μM = 502.35; KI 30 μM = 396.18*; KI 6 μM = 534.44*; KI 1 μM = 625.39 n.s., without TSH =184.85, values are expressed as cpm/ μg protein * = p<0.001). IHD at concentrations of 30 μM, 6 μM and 1 μM reduced iodide uptake by 77 %, 47 % and 33 % respectively. Under similar conditions KI caused the following inhibition: 66 % at 30 μM, 27 % at 6 μM; while at 1 μM the inhibition was not significant Western Blots were done for NIS and Tg. Treatment with IHD diminished Tg and NIS levels. Tg (TSH = 100 %, IHD 30 μM= 40 %, IHD 6 μM= 57 %, p<0.001); and NIS (TSH = 100 %, IHD 30 μM= 74%, IHD 6μM= 88 %, <0.001).
To further explore the molecular mechanism involved in IHD action, several mRNA level for thyroid specific proteins (TSP) were measured by semiquantitative RT-PCR. Table 1 shows that the pre-treatment of FRTL-5 cells with KI caused a significant reduction on TSP mRNA levels. This inhibition was relieved in some cases by MMI (10-3M) demonstrating
that an organic iodocompound is required in this action. When the cells were treated with IHD, an inhibition of TSP mRNA were also observed. While IHD exerts its effect in the presence of MMI indicating that its effect is independent of the iodide which could be released from its dehalogenation, the effect of the halogen is reversed in some cases by the
presence of the antithyroid drug, showing that iodide must be organified in order to exert its effect.
Conclusion: These findings indicate that IHD reproduces the effects of excess iodide and support its role in the autoregulatory mechanism.
