Living Reference Work Entry

Endocrinology of the Testis and Male Reproduction

Part of the series Endocrinology pp 1-46

Date: Latest Version

Gonadotrophin Receptors

  • Livio CasariniAffiliated withUnit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia
  • , Ilpo HuhtaniemiAffiliated withFaculty of Medicine, Department of Surgery & Cancer, Imperial College London
  • , Manuela SimoniAffiliated withUnit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia
  • , Adolfo Rivero-MüllerAffiliated withDepartment of Physiology, Institute of Biomedicine, University of Turku

Abstract

The two gonadotrophin receptors (GnRs), luteinizing hormone receptor (LHCGR) and follicle-stimulating receptor (FSHR), belong to the glycoprotein hormone receptor subgroup of type A G protein-coupled receptors (GPCRs). LHCGR binds specifically the two structurally similar gonadotrophins, luteinizing hormone (LH) and human chorionic gonadotrophin (hCG), and FSHR binds follicle-stimulating hormone (FSH). The receptors reside on plasma membrane and transmit the gonadotrophin signal to target cells using the classical Gs/adenylyl cyclase/cyclic AMP/protein kinase A signaling cascade. Other signaling pathways (e.g., inositol phosphate, calcium) are activated at pharmacological hormone concentrations or at high receptor density. LHCGR is expressed in testicular Leydig cells and in ovarian theca, luteinizing granulosa and luteal cells. FSHR is expressed in testicular Sertoli cells and ovarian granulosa cells. LHCGR activation stimulated Leydig cell steroidogenesis, in particular testosterone production, while FSHR maintains Sertoli cell metabolism, thereby indirectly stimulating spermatogenesis. Recent basic research, using GnR, expressing cells in vitro and genetically modified mice in vivo, has elucidated novel aspects of the molecular mechanisms of gonadotrophin receptor function. The crystal structure of GnRs has also been partly resolved. Numerous inactivating and activating GnR mutations that have been discovered in patients have unraveled the molecular basis of hypogonadism and other aberrations of reproductive endocrine functions. The purpose of this chapter is to review the recent trends of GnR research and how it has elucidated the molecular mechanisms of GnR function and the role of GnR in human reproductive physiology and pathophysiology.

Keywords

FSH Gonadotrophins hCG LH Polymorphism