Thyroid-Stimulating Hormone/Luteinizing Hormone/Follicle-Stimulating Hormone Receptors

Abstract

The thyroid-stimulating hormone receptor (TSHR), luteinizing hormone receptor (LHCGR), and follicle-stimulating hormone receptor (FSHR) are collectively referred to as the glycoprotein hormone receptors because they bind structurally similar glycoprotein hormones. The glycoprotein hormones consist of the pituitary thyroid-stimulating hormone (thyrotropin, TSH), luteinizing hormone (lutropin, LH), and follicle-stimulating hormone (follitropin, FSH) as well as the chorionic gonadotropin (choriogonadotropin, CG) placental hormone. The glycoprotein hormones are each composed of two dissimilar subunits (α and β) that are noncovalently associated. Within a given species, the α-subunit is identical and the β-subunits are distinct but homologous. Due to the largely similar nature of LHβ and CGβ, the LHCGR binds either LH or CG. The binding specificity of LH/CG to the LHCGR, FSH to the FSHR, and TSH to the TSHR is fairly strict. However, in some cases, extremely high levels of hormone can cause activation of the inappropriate receptor. Because the LHCGR and FSHR are localized primarily to the gonads, these two receptors are also referred to as the gonadotropin receptors. The glycoprotein hormone receptors belong to the family A (rhodopsin-like) of G protein-coupled receptors (GPCRs). However, they share the relatively unique feature of having a large extracellular domain that mediates high affinity binding of the hormone. In spite of their different physiological roles, the glycoprotein hormone receptors share a similar structural organization and mechanism of action.