ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2017) 49 S3.3 | DOI: 10.1530/endoabs.49.S3.3

Somatostatin receptors: news in the pituitary, lessons for the periphery

Justo Pastor Castaño


Spain.


The pituitary has been classically considered the ‘Master Gland’, owing to its ability to regulate the function of the other endocrine glands of the body. However, the hypophysis also served over the years as a master, guiding example to enlighten multiple fields of experimental biology and medicine, from classic physiology to modern cell biology, biochemistry and molecular biology. Somatostatin and its receptors (sst1-5) comprise a classic regulatory system, initially discovered and characterized at the hypothalamo-pituitary interface, which subsequently expanded to influence multiple bodily functions, from neurotransmission to digestive function and metabolic homeostasis, and also tumour biology. In this scenario, our group discovered an aberrantly spliced variant of sst5, sst5TMD4, which lacks 3 of the typical 7 transmembrane domains of GPCRs, but retains unique functional abilities and tisular and subcellular distribution. Initial studies revealed sst5TMD4 overexpression in pituitary tumors, particularly in acromegaly, where its presence is associated to a reduced response to somatostatin analogues, both in vitro and in vivo, and is linked to enhanced aggressiveness features, such as cell proliferation in vitro and tumor invasion in vivo. These findings led us to explore the possible presence and activity of sst5TMD4 in other hormone-related tumors. Interestingly, a series of collaborative studies demonstrated that this truncated receptor is overexpressed in multiple tumors and cancers, including, so far, breast cancer, pancreatic neuroendocrine tumors, poorly differentiated thyroid cancer, medullary thyroid carcinoma, and prostate cancer. In these pathologies, studies on patient samples and clinical features, an on tumor-derived primary cells or model cell lines have demonstrated that sst5TMD4 presence is directly linked to enhanced aggressiveness features, such as increased cell proliferation, migration and invasion, hormonal secretion, etc. Further analysis on the molecular underpinnings of these observed features have revealed a number of activated oncogenic or inactivated tumor-suppressing pathways and molecular players, some of which seem to be shared by most tumor types studied, whereas others seem to be unique for a given type of tumor/cancer. These results, coupled to our observation that other misspliced variants related to pituitary pathophysiology (namely, In1-grelin and GHS-R1b) are also present in the same tumors prompted us to study the splicing machinery. Of note, ongoing studies have revealed that the splicing machinery is dysregulated in these pathologies. Thus, the pituitary served, once again, to pave the way to scientific discovery for the periphery.

Article tools

My recent searches

No recent searches.