Thyroid hormones act as mitogenic and pro survival factors in rat ovarian follicles.

Purpose: Thyroid disorders are clinically associated with impaired fertility in women, and these abnormalities can be improved by restoring the euthyroid state. The exact mechanisms of thyroid effect on female fertility are not well known; however, it is conceivable that thyroid hormones (THs) might act on ovarian physiology via receptors in granulosa cells. This work is aimed at evaluating the effects of THs on non-tumoral granulosa cells and follicles.

Thyroid hormones and tendon: current views and future perspectives. Concise review.

Thyroid hormones (THs) T3 and T4, play an essential role in the development and metabolism of many tissues and organs, and have profound metabolic effects in adult life. THs action is mediated mainly by the thyroid hormone receptor (TRs) which seem to be ubiquitous. To-date thyroid-associated disease are not thought to be related in tendinopathies and tendons tears.

p53 Stabilization induces cell growth inhibition and affects IGF2 pathway in response to radiotherapy in adrenocortical cancer cells.

Adrenocortical carcinoma (ACC) is a very rare endocrine tumour, with variable prognosis, depending on tumour stage and time of diagnosis. However, it is generally fatal, with an overall survival of 5 years from detection. Radiotherapy usefulness for ACC treatment has been widely debated and seems to be dependent on molecular alterations, which in turn lead to increased radio-resistance.

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 (T(3)) protects rat ovarian granulosa cells from chemotherapy-induced apoptosis.

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 sacrificed.

Rosiglitazone induces autophagy in H295R and cell cycle deregulation in SW13 adrenocortical cancer cells.

Thiazolidinediones, specific peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands, used in type-2 diabetes therapy, show favourable effects in several cancer cells. In this study we demonstrate that the growth of H295R and SW13 adrenocortical cancer cells is inhibited by rosiglitazone, a thiazolidinediones member, even though the mechanisms underlying this effect appeared to be cell-specific. Treatment with GW9662, a selective PPAR-γ-inhibitor, showed that rosiglitazone acts through both PPAR-γ-dependent and -independent mechanisms in H295R, while in SW13 cells the effect seems to be independent of PPAR-γ.

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.

The thyroid hormone T3 improves function and survival of rat pancreatic islets during in vitro culture.

Ex vivo islet cell culture in the presence of stimulating factors prior to transplantation is considered a good strategy in contrast to the short conclusion of islets transplantation. Previously, we demonstrated how T3 can increase b-cell function via specific activation of Akt; therefore we hypothesized that thyroid hormone T3 can be considered a promising candidate for the in vitro expansion of islet cell mass. Rat pancreatic islets have been isolated by the collagenase digestion and cultured in the presence or not of the thyroid hormone T3 10⁻⁷ M.

Mitotane sensitizes adrenocortical cancer cells to ionizing radiations by involvement of the cyclin B1/CDK complex in G2 arrest and mismatch repair enzymes modulation.

Mitotane inhibits steroid synthesis by an action on steroidogenic enzymes, as 11beta-hydroxylase and cholesterol side chain cleavage. It also has a cytotoxic effect on the adrenocortical cells and represents a primary drug used in the adrenocortical carcinoma (ACC). H295R and SW13 cell lines were treated with mitotane 10(-5) M and ionizing radiations (IR) in combination therapy, inducing an irreversible inhibition of cell growth in both adrenocortical cancer cells.

Proteomic profiles in hyperandrogenic syndromes.

Background: Polycystic ovary syndrome (PCOS) and congenital adrenal hyperplasia (CAH) represent the most common causes of hyperandrogenism. Although the etiopathogeneses of these syndromes are different, they share many clinical and biochemical signs, such as hirsutism, acne, and chronic anovulation. Experimental data have shown that peripheral T-lymphocytes function as molecular sensors, being able to record molecular signals either at staminal and mature cell levels, or hormones at systemic levels.

Thyroid hormones induce cell proliferation and survival in ovarian granulosa cells COV434.

Numerous evidences indicate that thyroid hormones exert an important role in the regulation of the reproductive system in the adult female. Although a clear demonstration of the thyroid-ovarian interaction is still lacking, it is conceivable that thyroid hormones might have a direct role in ovarian physiology via receptors in granulosa cells. In this study we analyzed if thyroid hormone treatment could affect cell proliferation and survival of COV434 cells.

The TRbeta1 is essential in mediating T3 action on Akt pathway in human pancreatic insulinoma cells.

Thyroid hormone action, widely recognized on cell proliferation and metabolism, has recently been related to the phosphoinositide 3 kinase (PI3K), an upstream regulator of the Akt kinase and the involvement of the thyroid hormone receptor beta1 has been hypothesized. The serine-threonine kinase Akt can regulate various substrates that drive cell mass proliferation and survival. Its action has also been characterized in pancreatic beta-cells.

Mitotane increases the radiotherapy inhibitory effect and induces G2-arrest in combined treatment on both H295R and SW13 adrenocortical cell lines.

Mitotane, 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane (o,p'-DDD) is an agent with adrenotoxic effect, which is able to block cortisol synthesis. This drug and radiotherapy are used also in adrenal cancer treatment even if their biological action in this neoplasia remains unknown. We investigated the effects of o,p'-DDD and ionizing radiations (IR) on cell growth inhibition and cell cycle perturbation in H295R and SW13 adrenocortical cancer cells.

Modulation of proteomic profile in H295R adrenocortical cell line induced by mitotane.

Mitotane, 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chloro-phenyl) ethane (o,p'-DDD), is a compound that represents the effective agent in the treatment of the adrenocortical carcinoma (ACC), able to block cortisol synthesis. In this type of cancer, the biological mechanism induced by this treatment remains still unknown. In this study, we have already shown a greater impairment in the first steps of the steroidogenesis and recognized a little effect on cell cycle.

Proteomic analysis of peripheral T lymphocytes, suitable circulating biosensors of strictly related diseases.

T lymphocytes and/or their subpopulations from peripheral blood may represent molecular sensors to be used for the evaluation of gene expression modification in physiological and pathological conditions, providing a unique and easily available biological model for integrated studies of gene expression in humans. In this study, a proteomic approach was applied to evaluate the association between changes in T cell protein expression patterns and specific diseased conditions. In particular, two hyperandrogenic syndromes were studied, sharing many clinical and biochemical signs: polycystic ovary syndrome (PCOS) and congenital adrenal hyperplasia (CAH).

Increased metastatic lymph node 64 and CYP17 expression are associated with high stage prostate cancer.

The metastatic lymph node 64 (MLN64), which is localized in the human chromosome 17, encodes a protein with strong homology with steroidogenic acute regulatory protein. Its overexpression in human breast carcinomas and MLNs led to the hypothesis that this protein could be involved in intraneoplastic steroidogenesis. In the present study, we investigated the expression of MLN64 in prostate cancer, another hormone-dependent tumor, and compared its expression with that of CYP17, the gene encoding for the key enzyme of androgen synthesis.

O(2/3) exposure inhibits cell progression affecting cyclin B1/cdk1 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 anti-tumoral treatment. Given the physiochemical properties of O(2/3) gas mixture including fairly low aqueous solubility and spreading, and the interesting perspective of hyperoxia, we analyzed the inhibitory effect of O(2/3) treatment on two human neuroblastoma cell lines (SK-N-SH and SK-N-DZ). In this study, we demonstrated that O(2/3) treatment was able to induce cell growth inhibition and cell cycle perturbation in both cell lines.

3,3',5-Triiodo-L-thyronine inhibits ductal pancreatic adenocarcinoma proliferation improving the cytotoxic effect of chemotherapy.

The pancreatic adenocarcinoma is an aggressive and devastating disease, which is characterized by invasiveness, rapid progression, and profound resistance to actual treatments, including chemotherapy and radiotherapy. At the moment, surgical resection provides the best possibility for long-term survival, but is feasible only in the minority of patients, when advanced disease chemotherapy is considered, although the effects are modest. Several studies have shown that thyroid hormone, 3,3',5-triiodo-l-thyronine (T(3)) is able to promote or inhibit cell proliferation in a cell type-dependent manner.

Thyroid hormone receptor TRbeta1 mediates Akt activation by T3 in pancreatic beta cells.

It has recently been recognized that thyroid hormones may rapidly generate biological responses by non-genomic mechanisms that are unaffected by inhibitors of transcription and translation. The signal transduction pathways underlying these effects are just beginning to be defined. We demonstrated that thyroid hormone T3 rapidly induces Akt activation in pancreatic beta cells rRINm5F and hCM via thyroid hormone receptor (TR) beta1.

Fractionated ionizing radiation exposure induces apoptosis through caspase-3 activation and reactive oxygen species generation.

Background: Radiation therapy (RT) is a well established therapeutic modality for the treatment of solid tumors. In particular, post-operative RT is considered the standard treatment adjuvant to surgery since its ability to prolong median survival of patients with malignant astrocytoma has been shown; nevertheless the ionizing radiation (IR) treatment fails in a considerable number of astrocytoma patients.

Materials And Methods: Using an ADF human astrocytoma cell line the molecular mechanisms involved in the DNA damage induced by fractionated irradiation (FIR) and single IR treatment have been investigated.

3,5,3'-triiodothyronine (T3) is a survival factor for pancreatic beta-cells undergoing apoptosis.

3,5,3'-triiodothyronine (T3) is essential for the growth and the regulation of metabolic functions, moreover, the growth-stimulatory effect of T3 has largely been demonstrated and the pathways via which T3 promotes cell growth have been recently investigated. Type 1 diabetes (T1D) is due to the destruction of beta-cells, which occurs even through apoptosis. Aim of our study was to analyze whether T3 could have an antiapoptotic effect on cultured beta-cells undergoing apoptosis.

3,5,3'-Triiodo-L-thyronine enhances the differentiation of a human pancreatic duct cell line (hPANC-1) towards a beta-cell-Like phenotype.

The thyroid hormone, 3,5,3'-Triiodo-L-thyronine (T3), is essential for growth, differentiation, and regulation of metabolic functions in multicellular organisms, although the specific mechanisms of this control are still unknown. In this study, treatment of a human pancreatic duct cell line (hPANC-1) with T3 blocks cell growth by an increase of cells in G(0)/G(1) cell cycle phase and enhances morphological and functional changes as indicated by the marked increase in the synthesis of insulin and the parallel decrease of the ductal differentiation marker cytokeratin19. Expression analysis of some of the genes regulating pancreatic beta-cell differentiation revealed a time-dependent increase in insulin and glut2 mRNA levels in response to T3.