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SUMMARY
[4-14C]Oestradiol-17β, [4-14C]oestrone, Na[6,7-3H]oestradiol-17β-glucuronide and Na[6,7-3H]oestrone sulphate were injected into a Graafian follicle of two mares and a donkey after cannulation of the ovarian vein. Radioactivity was measured in follicular fluid and ovarian venous blood at different intervals after injection and in tissue and interstitial fluid at the end of the operation. Both free and conjugated oestrogens were retained to a great extent in the follicle, in the presence of constant production of endogenous oestrogens. Only a small portion of the oestrogen released from the follicle passed directly into the ovarian venous blood; a larger portion entered the effluent blood indirectly, through interstitial fluid and tissue. The conjugates, particularly the glucuronide, seemed to be excluded from the cells and accumulated in the interstitial fluid.
The role of binding of oestrogens to fluid proteins in the retention of oestrogen in follicular fluid is discussed.
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Instituto de Investigaciones Biomédicas (BIOMED), Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Laboratorio de Radioisótopos, Area de Investigación, Departamento de Química Biológica, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), Av. A. Moreau de Justo 1600, 3er piso, 1107AFF Buenos Aires, Argentina
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Instituto de Investigaciones Biomédicas (BIOMED), Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Laboratorio de Radioisótopos, Area de Investigación, Departamento de Química Biológica, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), Av. A. Moreau de Justo 1600, 3er piso, 1107AFF Buenos Aires, Argentina
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We have shown in vitro that thyroid hormones (THs) regulate the balance between proliferation and apoptosis of T lymphoma cells. The effects of THs on tumor development have been studied, but the results are still controversial. Herein, we show the modulatory action of thyroid status on the in vivo growth of T lymphoma cells. For this purpose, euthyroid, hypothyroid, and hyperthyroid mice received inoculations of EL4 cells to allow the development of solid tumors. Tumors in the hyperthyroid animals exhibited a higher growth rate, as evidenced by the early appearance of palpable solid tumors and the increased tumor volume. These results are consistent with the rate of cell division determined by staining tumor cells with carboxyfluorescein succinimidyl ester. Additionally, hyperthyroid mice exhibited reduced survival. Hypothyroid mice did not differ significantly from the euthyroid controls with respect to these parameters. Additionally, only tumors from hyperthyroid animals had increased expression levels of proliferating cell nuclear antigen and active caspase 3. Differential expression of cell cycle regulatory proteins was also observed. The levels of cyclins D1 and D3 were augmented in the tumors of the hyperthyroid animals, whereas the cell cycle inhibitors p16/INK4A (CDKN2A) and p27/Kip1 (CDKN1B) and the tumor suppressor p53 (TRP53) were increased in hypothyroid mice. Intratumoral and peritumoral vasculogenesis was increased only in hyperthyroid mice. Therefore, we propose that the thyroid status modulates the in vivo growth of EL4 T lymphoma through the regulation of cyclin, cyclin-dependent kinase inhibitor, and tumor suppressor gene expression, as well as the stimulation of angiogenesis.