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

A.J. KLECHA; M.L. BARREIRO ARCOS; S. LANDA; S. GARCÍA; C. PIROLA; A.M. GENARO; G.A. CREMASCHI

Paris

Congreso; 14th International Thyroid Congress.; 2010

European Thyroid Association, American Thyroid Association, Asia & Oceania Thyroid Association and Latin American Thyroid Society

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 expressing TRH were obtained by pronuclear injection of a gene construct containing the TRH precursor cDNA. To characterize the thyroid status of these mice we measured diencephalic TRH and serum TSH and total thyroid hormones by radioimmunoassay. Then, we analyzed the lymphocyte activity measuring proliferation by tritiated thymidine incorporation and T helper (Th-) 1 and 2 cytokine production by ELISA. We compared these results with those obtained modulating thyroid 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. Immune responses evaluated in these mice showed that TRH levels correlate with a higher T and B lymphocyte proliferation in response to selective mitogen stimulation. Additionally, these effects were accompanied by an increment in the release of Th1 cytokines and of interleukin (IL-) 6, but not of other Th2 (IL-4 and IL-10) or the pro-inflammatory tumor necrosis factor alpha (TNF-a) cytokines. However, experimental hypothyroidism led to a decrease in lymphocyte reactivity and in the secretion of the Th1 cytokines interferon gamma (IFN-g) and IL-2. On the other hand, hyperthyroid mice displayed increased lymphocyte activity. Conclusions: These results show that the transgenic mice obtained, did not develop other thyroid axis alterations and suggest that augmentation of hypothalamic releasing hormone leads to the increase of T and B cell responses, unlike the facts observed in hypothyroid conditions.