Endocrine Abstracts

Background: It has recently been recognized that thyroid hormones may rapidly generate biological responses by nongenomic mechanisms that are unaffected by inhibitors of transcription and translation. The signal transduction pathways for these effects are just beginning to be defined.Aim: To examine the specific pathway via which T3 can activate Akt in pancreatic beta cells and to understand further the possible implication of a nongenomic action of T3 i...

IntroductionAdrenal insufficiency is a clinical condition that leads to depletion of glucocorticoids, mineralocorticoids and androgens. While in men adrenal androgen deficiency is not clinically significant for testicular testosterone synthesis, in women so far androgen treatment is suggested for the reduction of libido and depression. However, no data is currently available on female sexual function.Primary endpoints<p class="...

Mitotane (MTT) currently represents the treatment of choice for adrenocortical carcinoma (ACC). Clinical evidence shows the occurrence of hypogonadism following treatment with this drug, observed more frequently in male patients. The aim of the study, therefore, was to evaluate the impact of MTT treatment on male gonadal function on adult CD1 mice. At the end of the 45 days of treatment, testes were collected for morphological examination, and a blood sample of each animal was...

Biochemical function of adrenal masses is currently based on 1 mg post-overnight dexamethasone suppression test (pDST). Several approaches are recently developed, in order to reduce false positive/negative samples, only in retrospective series. They are based on the correlation of some different parameters, i.e. late-night salivary cortisol (LNSC) vs serum and salivary cortisol pDST; LNSC vs serum and salivary cortisol and serum dexamethasone pDST; LNSC and cortisone vs serum ...

Adrenocortical Cancer (ACC) is characterized by an increased production of insulin-like growth factor 2 (IGF2) and by estrogen receptor (ER) α up-regulation. Aim of this study was to define IGF2 and estrogen signaling interactions in ACC, in order to give new indications for a better therapy. To this aim we used H295R cells and human ACC tissues which display common features: IGF2 activation of downstream effector pathways and over-expression of estrogen-related genes inc...

Background: Actually mitotane is an adrenal-specific agent employed in the treatment of adrenocortical carcinoma (ACC), and although it has been used for several decades, its exact mechanism of action, remain to be fully elucidated. Some authors reported that mitotane affected in vitro the multidrug resistance gene mdr-1/P-glycoprotein. MRP1, belonging a multidrug resistance protein family, exerts a chemo-resistance activity in many type of cancer leading to the failure...

It is clinically evident that women suffering from thyroid disorders are associated with frequent occurrence of menstrual disturbances and impaired fertility, and these abnormalities are improved by restoring the euthyroid state. The exact mechanism for such reproductive aberrations is not well known; however, it is conceivable that thyroid hormones might have a direct role in ovarian physiology via receptors in granulosa cells. We evaluated the effect of thyroid hormones (T<s...

Background: Mitotane, 1,1-dichloro-2-(o chlorophenyl) -2- (p-chloro phenyl) ethane (o,p′-DDD) is a compound which represents the effective agent in the treatment of the adrenocortical carcinoma (ACC), able to block cortisol synthesis. Nevertheless the biological mechanism induced by this treatment in this cancer remains unknown. Recently, there has been a strong interest in applying proteomics to foster a better understanding of disease proces...

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 β1 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 β-cells. We previously demonstrated tha...

Background: Mitotane,(o,p’-DDD)is a compound with potent adrenotoxic effect and is able to block cortisol synthesis by inhibiting 11β-hydroxylation and cholesterol chain cleavage. For these reasons, mitotane was widely used in the treatment of adrenocortical cancer. Nevertheless the biological mechanism induced by these treatments in this cancer cells remain unknown.Aim: To study whether the o,p’-DDD could increase the susceptibility to th...