Endocrine Abstracts

Olfactory marker protein (OMP) is a marker of olfactory receptor-mediated chemoreception, even outside the olfactory system. Here, we report that OMP expression in the pituitary gland plays a role in basal and thyrotropin-releasing hormone (TRH)-induced prolactin (PRL) production and secretion. We found that OMP was expressed in human and rodent pituitary glands, especially in PRL-secreting lactotrophs. OMP knockdown in GH4 rat pituitary cells increased PRL production and secr...

Despite the increasing evidence on the relevance of the actin binding protein filamin A (FLNA) in determining an efficient intracellular response to somatostatin analogs (SSA) in pituitary tumors, there is a gap in the knowledge on the mechanisms regulating FLNA itself. FLNA is phosphorylated by PKA on Ser2152 located in a FLNA region crucial for SST2 or partner proteins binding. Although cAMP/PKA pathway plays a crucial role in GH-secreting tumors pathogenesis, the...

Aim: To assess whether E-cadherin expression levels in somatotropinomas were associated with the response to somatostatin analogues (SSAs) therapy in patients with acromegaly.Methods: In this retrospective study, 56 acromegaly patients that underwent transsphenoidal surgery were evaluated. All patients were treated preoperatively with SSAs (octreotide or lanreotide) for at least 6 months. Responsiveness to SSAs was evaluated by percent IGF-1 reduction af...

The tumorigenesis of Cushing’s disease is characterized by somatic mutations in the USP8 gene in almost half of the cases. USP8 encodes for ubiquitin specific protease 8, a deubiquitinase that rescues proteins involved in the regulation of ACTH synthesis in corticotroph cells. In the present study we tested the antisecretory and antiproliferative efficacy of a commercially available specific USP8 inhibitor (IC50 3.1 μM USP8; >90 μM USP7) in immortalized muri...

Recently, somatic, heterozygous mutations in the gene encoding the deubiquitinase USP8 have been identified in 30–60% of corticotroph tumors. These mutations were found to hinder binding of 14-3-3 proteins, increasing its deubiquitinating activity. One substrate is Epidermal Growth Factor Receptor (EGFR), USP8 triggers EGFR recycling and increased EGFR signaling. However, tumors harboring mutations in USP8 are smaller than WT tumors, raising the debate if EGFR, as a poten...

Pituitary adenomas (PA), as well as pheochromocytomas and paragangliomas, are neuroendocrine tumors that arise from cells derived from the pituitary, adrenal and extra-adrenal nervous system, respectively. Recent studies have identified a growing series of susceptibility genes for these pathologies. Some genes may be associated with the development of both types of pathologies, as it is the case for succinate dehydrogenase complex genes, while, PAs have not been reported to da...

Non-functioning pituitary adenomas (NFPAs) represent the most common type of pituitary adenomas. NFPAs are mostly macroadenomas (>1 cm) at diagnosis and, despite their lack of functional hormone hypersecretion, are associated to severe comorbidities related to mass effect (i.e. headaches, visual defects and hypopituitarism). Transsphenoidal surgery is the mainstay of NFPAs treatment, although it is often not definitive, mainly due to the invasion of neighboring intracrania...

The somatostatin receptor 5 (sst5) and its truncated splicing variants (sst5TMD5, sst5TMD4) are considered putative biomarkers that can predict pharmacological response or aggressiveness in several endocrine-related pathologies, such as acromegaly. sst5 is encoded by a gene, SSTR5, that lacks introns within its coding sequence, and hence, the splicing variants identified are generated by non-canonical splicing events. However, the mechanisms underlying their genesis a...