Thyroid Hormone T3 Counteracts STZ Induced Diabetes in Mouse

This study intended to demonstrate that the thyroid hormone T3 counteracts the onset of a Streptozotocin (STZ) induced diabetes in wild type mice. To test our hypothesis diabetes has been induced in Balb/c male mice by multiple low dose Streptozotocin injection; and a group of mice was contemporaneously injected with T3. After 48 h mice were tested for glucose tolerance test, insulin serum levels and then sacrified. Whole pancreata were utilized for morphological and biochemical analyses, while protein extracts and RNA were utilized for expression analyses of specific molecules. The results showed that islets from T3 treated mice were comparable to age- and sex-matched control, untreated mice in number, shape, dimension, consistency, ultrastructure, insulin and glucagon levels, Tunel positivity and caspases activation, while all the cited parameters and molecules were altered by STZ alone. The T3-induced pro survival effect was associated with a strong increase in phosphorylated Akt. Moreover, T3 administration prevented the STZ-dependent alterations in glucose blood level, both during fasting and after glucose challenge, as well as in insulin serum level. In conclusion we demonstrated that T3 could act as a protective factor against STZ induced diabetes

O2/3 exposure inhibits cell progression affecting cyclin B1/cdk 1 activity in SK-N-SH while induces apoptosis in SK-N-DZ neuroblastoma cells

In search for innovative therapeutic agents for children neuroblastoma, the oxygen therapy could be considered an alternative antitumoral treatment. Given the physiochemical properties ofO2/3 gas mixture including fairly low aqueous solubility and spreading, and the interesting perspective of hyperoxia, we analyzed the inhibitory effect ofO2/3 treatment on two human neuroblastoma cell lines (SK-N-SH and SK-N-DZ). In this study, we demonstrated thatO2/3 treatment was able to induce cell growth inhibition and cell cycle perturbation in both cell lines. We observed an arrest at G2 phase, accompanied by an alteration in the expression and localization of cyclin B1/cdk1 complex and a reduction in its activity in SK-N-SH cells. This reduction was consistent with the increase in both Wee1 and chk1 protein levels. On the contrary, O2/3 induced apoptosis in SK-N-DZ cells via caspase 3 activation and Poly ADP-ribose polymerase-1 (PARP) cleavage, associated with an increase in the pro-apoptotic Bax protein. Consequently, we considered the possibility of improving the responsiveness to chemotherapeutic agents such as Cisplatin, Etoposide, and Gemcitabine in combination with O2/3 treatment. The combined treatments produced a stronger cell inhibitory effect than Cisplatin and Etoposide used alone in SK-N-SH cells.Onthe contrary, the combination data were not significantly different from O2/3 treatment alone in SK-N-DZ cells, thus suggesting that the obtained changes in cell growth inhibition were due to the effect of O2/3 alone

Thyroid hormones enhance growth and counteract apoptosis in human tenocytes isolated from rotator cuff tendons

[No abstract available

T-3 preserves ovarian granulosa cells from chemotherapy-induced apoptosis

Infertility is a dramatic and frequent side effect in women who are undergoing chemotherapy. Actual strategies are mainly focused on oocyte cryopreservation, but this is not always a suitable option. Considering the key role that granulosa cells play in follicle life, we studied whether thyroid hormone 3, 5, 3′-triiodothyronine (T3) protects rat ovarian granulosa cells from chemotherapy-induced apoptosis. To this aim, a cell line was established from fresh isolated rat granulosa cells and named rGROV. Cells were exposed to paclitaxel (PTX) and T3, and apoptosis, cell viability, and cell cycle distribution were analyzed under different conditions. First, the integrity of the steroidogenic pathway was demonstrated, and the presence of thyroid receptors, transporters, and deiodinases was confirmed by quantitative PCR. Cells were then exposed to PTX alone or contemporary to T3. MTT and TUNEL assays revealed that while there was a relevant percentage of dying cells when exposed to PTX (40-60%), the percentage was sensibly reduced (20-30%) in favor of living cells if T3 was present. Cell cycle analysis showed that cells exposed to PTX alone were first collected in G2 and then died by apoptosis; on the other hand, the T3 granted the cells to cycle regularly and survive PTX insult. In addition, western blot and FCM analyses confirmed that caspases activation, casp 3 and Bax, were downregulated by T3 and that Bcl2 and cyclins A and B together with cdk1 were upregulated by T3. In conclusion, we demonstrated that thyroid hormone T3 can counteract the lethal effect of taxol on granulosa cells. © 2012 Society for Endocrinology

Thyroid Hormones (T3 and T4): Dual Effect on Human Cancer Cell Proliferation

Several findings suggest that the patient's hormonal context plays a crucial role in determining cancer outcome. The exact nature of thyroid hormone action on tumour growth has not been established yet, in fact contrasting data show thyroid hormones have a promotory or an inhibitory action on cancer cell proliferation depending on the case. We hypothesized that not only tissue specificity, but also specific mutations occurring during tumoral development in different thyroid hormone cellular targets are responsible for this dual effect. To test our hypothesis we analysed, by time-course and bromodeoxyuridine assay, thyroid hormone effects on the proliferation of six cancer cell lines originating from the same tissue or organ but carrying different mutations (in phospho-inositide 3 kinase or β-catenin genes). The data obtained in this study show how mutations that affect the balance between degradation and stabilization of β-catenin assume a remarkable importance in determining the cell-specific thyroid hormone effect on cell growth