Thyroid status of transgenic mice overexpressing thyrotropin-releasing hormone (TRH) and its relantionship with lymphocyte activity”

ALICIA JUANA KLECHA; MARÍA LAURA BARREIRO ARCOS; SILVINA LANDA; SILVIA GARCÍA; CARLOS PIROLA; ANA MARÍA GENARO; GRACIELA A CREMASCHI

París

Congreso; 14th International Thyroid Congress.; 2010

Abstract: Summary: To investigate the participation of the different components of the thyroid axis, thyroid hormones(T3 and T4), thyrotropin (TSH) or thyrotropin realizing hormone (TRH) in regulation of immunity, mice over expressingTRH were obtained by pronuclear injection of a gene construct containing the TRH precursor cDNA. To characterize thethyroid status of these mice we measured diencephalic TRH and serum TSH and total thyroid hormones byradioimmunoassay. Then, we analyzed the lymphocyte activity measuring proliferation by tritiated thymidine incorporationand T helper (Th-) 1 and 2 cytokine production by ELISA. We compared these results with those obtained modulatingthyroid axis with thyroxin or propylthiouracil administration to induce hypo or hiperthyroidism in mice.Results: As it is shown in the following table, transgenic mice displayed higher diencephalic levels of TRH as expected,but similar serum levels of TSH and thyroid hormones than control mice.T3(ng%)T4(μg%)TSH(ng/ml)TRH(pg/mg protein)C57-Control 115 ± 6 3.9 ± 0.3 52.3 ± 3.3 472.8 ± 7.5C57-Transgenic 108 ± 4 4.4 ± 0.2 60.0 ± 4.1 1093.9 ± 4.7*Immune responses evaluated in these mice showed that TRH levels correlate with a higher T and B lymphocyteproliferation in response to selective mitogen stimulation. Additionally, these effects were accompanied by an incrementin the release of Th1 cytokines and of interleukin (IL-) 6, but not of other Th2 (IL-4 and IL-10) or the pro-inflammatorytumor necrosis factor alpha (TNF-a) cytokines. However, experimental hypothyroidism led to a decrease in lymphocytereactivity and in the secretion of the Th1 cytokines interferon gamma (IFN-g) and IL-2. On the other hand, hyperthyroidmice displayed increased lymphocyte activity.Conclusions: These results show that the transgenic mice obtained, did not develop other thyroid axis alterations andsuggest that augmentation of hypothalamic releasing hormone leads to the increase of T and B cell responses, unlike thefacts observed in hypothyroid conditions.Disclosure of Interest: None Declared