Endocrine Abstracts

ACTH is the product of proteolytic processing of its precursor, proopiomelanocortin (POMC) and, in turn, is subject to proteolytic degradation. Regulation of proteolysis is crucial to several intracellular processes, including protein activation and inactivation, and thus contributes to active peptide concentrations. The proteosome 26S/ubiquitin system (UPS) is the main, non-lisosomial intracellular proteolytic pathway and alterations to this system have been observed in both ...

Corticotropin-releasing hormone (CRH) is known to be produced and secreted by normal rat corticotropes and to contribute in a paracrine manner to POMC synthesis and ACTH secretion in these cells. The regulation of intrapituitary CRH however still has to be clarified.Aim: This study was to establish whether CRH gene expression can be measured in rat pituitaries in vitro and whether CRH modulates its own gene expression within the pitu...

Retinoic acid, a derivative of vitamin A, has recently yielded promising results in the treatment of Cushing’s disease (Pecori Giraldi et al. JCEM 2012). Its main site of action appears to be the tumoural corticotrope as retinoic acid inhibits POMC transcription and corticotrope proliferation (Paez-Pereda et al. JCI 2001). Studies on tumoural adrenal cell lines have revealed an additional inhibitory effect on cell proliferation and stimulated co...

An increased prevalence of acromegaly and pituitary tumors has recently been observed in high industrial density areas (Cannavò et al. J Endocrinol 2010) or after dioxin exposure (Pesatori et al. Eur J Endocrinol 2008). These data as well as vitro studies on endocrine disruptors (EDs) suggest that environmental pollutants may affect hormonal secretion and pituitary cell proliferation (Blake et al. Proc Soc Exp Biol...

Silibinin, a milk thistle extract with known hepatoprotective effects, has recently been shown to act upon tumoral corticotropes and revert the Cushingoid phenotype in an allograft mouse model (Riebold et al. 2015). Silbinin is known to inhibit HSP90 -a chaperone to the glucocorticoid receptor-thereby restoring sensitivity to glucocorticoid negative feedback in tumoral corticotropes. Aim of the present study was to assess the effect of silibinin on ACTH synthesis and ...

DNA methylation has recently been shown to play a role in postnatal as well as developmental gene regulation. Transfer and removal of methyl groups from CpG islands in the promoter region of specific genes has been associated with gene silencing or activation, respectively. POMC is known to present several methylation sites and demethylation of these sites has been shown to be linked to POMC expression by neuroendocrine tumors outside the pituitary.<p class="...

Retinoic acid, a major modulator of adrenal development and differentiation, has also been shown to inhibit ACTH secretion by tumoral corticotropes. Recent clinical trials in patients with Cushing’s disease revealed that retinoic acid exerts beneficial effects in these patients (1, 2). Of note, the decrease in cortisol secretion during retinoic acid administration was more pronounced than the change in ACTH levels (1) suggesting a direct action at adrenal level. Aim of th...