There are three anterior pituitary (TSH, LH, FSH) and one placental (human chorionic gonadotropin, hCG) heterodimeric glycoprotein hormones. These hormones share a common α-subunit and have distinct β-subunits, as illustrated in Figure 1. The α- and β-subunits are each stabilized by disulfide bonds, and disruption of these bonds by reducing agents alters the internal configuration of the peptide chains, causing dissociation of the heterodimer. It is the β-subunit that confers the specificity on the structure of the hormone so that each of the four heterodimers interacts only with its specific receptor. The one α and four β subunits that make up the four hormones each contain either one or two asparagineN-linked oligosaccharides. In addition, hCG has a carboxy terminal peptide extension, relative to the other β-subunits, that has four serine residues serving as O-linked glycosylation sites. These sites on hCG are not highly important in receptor binding and signal transduction, but serve to increase the in vivo half-life of the hormone and therefore its bioactivity. The N-linked oligosaccharides in hCG are important for biological activity and their removal results in the conversion of the active hormone into an antagonist that binds to the receptor but does not activate it.
Fig1. The subunit structure of the pituitary glycoprotein hormones. The three pituitary glycoprotein hormones, thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH), luteinizing hormone (LH), and the placental version of LH, human chorionic gonadotropin (hCG), all consist of two subunits. They share a common α-subunit (blue), which combines with a unique β-subunit to form each of the four active heterodimeric hormones. The positions of the N-glycosylated asparagine sites are indicated by the forks for each of the five subunit types; hCG is characterized by a C-terminal extension with O-glycosylated serine sites.
As discussed in some detail in Chapter 5, the biological role of TSH is to stimulate the synthesis and secretion of the thyroid hormones, thyroxine (T4) and T3, from the epithelial cells making up the follicles of the thyroid gland. Similarly, the important biological roles of FSH and LH throughout the reproductive system in males and females. Also, hCG, which is initially produced by the human trophoblast upon implantation in the uterus, mimics the actions of LH and is essential for maintenance of pregnancy in its early stages.
