Impact of G protein-coupled receptor heteromers in endocrine systems

•Homo/heteromerization can diversify GPCR function.•We explore the in vitro and in vivo significance of GPCR heteromers, with a focus on endocrine-related processes.•We describe the current outlook for pharmacological interventions and current/future treatments for GPCR heteromers.

The fine-tuning of endocrine homeostasis is regulated by dynamic receptor mediated processes. The superfamily of G protein-coupled receptors (GPCRs) have diverse roles in the modulation of all endocrine axes, thus understanding the mechanisms underpinning their functionality is paramount for treatment of endocrinopathies. Evidence over the last 20 years has highlighted homo and heteromerization as a key mode of mediating GPCR functional diversity. This review will discuss the concept of GPCR heteromerization and its relevance to endocrine function, detailing in vitro and in vivo evidence, and exploring current and potential pharmacological strategies for specific targeting of GPCR heteromers in endocrine heath and disease.