Aberrant hormone receptors regulate a wide spectrum of endocrine tumors.

in The lancet. Diabetes & endocrinology by André Lacroix, Isabelle Bourdeau, Fanny Chasseloup, Peter Kamenický, Antoine-Guy Lopez, Estelle Louiset, Hervé Lefebvre

TLDR

  • The study looks at how certain proteins called G-protein coupled receptors (GPCRs) are expressed in different types of tumors in the body. These proteins can help the tumors work too well, which can be harmful. The study suggests that targeting these proteins with special imaging techniques could help identify and treat these tumors.

Abstract

Aberrant G-protein coupled receptor (GPCR) expression is highly prevalent in cortisol-secreting primary bilateral macronodular adrenal hyperplasia (PBMAH) and unilateral adenomas. The aberrant expression of diverse GPCRs and their ligands play an important role in the over-function of various endocrine tumours. Examples include aberrant expression of MC2R, 5-HT4R, AVPR1A, LHCGR, and GnRHR in primary aldosteronism; GCGR, LHCGR, and 5-HT4R in phaeochromocytomas and paragangliomas; TRHR, GnRHR, GIPR, and GRP101 in pituitary somatotroph tumours; AVPR2, D2DR, and SSTR5 in pituitary corticotroph tumours; GLP1R, GIPR, and somatostatin receptors in medullary thyroid carcinoma; and SSTRs, GLP1R, and GIPR in other neuroendocrine tumours. The genetic mechanisms causing the ectopic expression of GIPR in cortisol-secreting PBMAHs and unilateral adenomas have been identified, but distinct mechanisms are implicated in other endocrine tumours. Development of functional imaging targeting aberrant GPCRs should be useful for identification and for specific therapies of this wide spectrum of tumours. The aim of this review is to show that the regulation of endocrine tumours by aberrant GPCR is not restricted to cortisol-secreting adrenal lesions, but also occurs in tumours of several other organs.

Overview

  • The study focuses on the aberrant expression of G-protein coupled receptors (GPCRs) in various endocrine tumors, including primary bilateral macronodular adrenal hyperplasia (PBMAH), unilateral adenomas, and tumors of other organs. The study aims to show that the regulation of endocrine tumors by aberrant GPCR is not limited to cortisol-secreting adrenal lesions but also occurs in tumors of several other organs. The study uses a review format to summarize the existing literature on the topic.

Comparative Analysis & Findings

  • The study does not provide a direct comparative analysis of outcomes under different experimental conditions or interventions. However, the study compares the aberrant expression of diverse GPCRs and their ligands in various endocrine tumors, including primary aldosteronism, phaeochromocytomas and paragangliomas, pituitary somatotroph tumours, corticotroph tumours, medullary thyroid carcinoma, and other neuroendocrine tumors. The study identifies distinct mechanisms for the ectopic expression of GIPR in cortisol-secreting PBMAHs and unilateral adenomas, but does not provide a direct comparison of these mechanisms in other endocrine tumors.

Implications and Future Directions

  • The study highlights the importance of aberrant GPCR expression in the over-function of various endocrine tumors. The study suggests that the development of functional imaging targeting aberrant GPCRs could be useful for the identification and specific therapies of this wide spectrum of tumors. The study identifies several limitations, including the lack of a direct comparative analysis of outcomes under different experimental conditions or interventions and the need for further research to identify the specific mechanisms for the ectopic expression of GIPR in other endocrine tumors.
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