Molecular and functional insights into gonadotropin hormone receptor dimerization and oligomerization

The gonadotropin hormones, follicle stimulating hormone and luteinizing hormone, are essential for reproduction. They work in concert to control multiple aspects of gonadal function to ultimately produce meiotically competent and fertilizable gametes, provide the optimal endometrial environment and support for implantation and maintain pregnancy via progesterone production throughout the first trimester of pregnancy. These complex and multidimensional functions are mediated via the gonadotropin hormone receptors, luteinizing hormone receptor and follicle stimulating hormone receptor, Class A G protein-coupled receptors (GPCR), which couple to multiple G protein-dependent and independent signal pathways to control these physiological processes. Over the last two decades, a plethora of experimental evidence has shown that GPCRs can associate to form dimers and oligomers. This association provides a means of mediating the diverse functional requirements of a single receptor subtype and for the gonadotropin hormone receptors, has been shown to alter the pharmacology and signal activation profile of these receptors. This review will detail the historical and current evidence detailing the formation of gonadotropin hormone receptor homomers and heteromers. We will discuss the functional insights gained from in vitro and in vivo studies, and the potential impact in modulating reproductive health and disease.