7 - Structures of Free α- and β-Subunits

Abstract

In pregnancy serum, free β-subunit is primarily derived from the dissociation of hCG-H and regular hCG. The free β-subunit is detected in serum and urine samples. In most cases, excess amounts of β-subunit are made in hydatidiform moles or choriocarcinoma cells. This is secreted as free β-subunit. Cancer cells retro-differentiate or are otherwise transformed and express the β-subunit of hCG. The α-subunit expression is limited. This might lead to free β-subunit production by cancer cells. hCG is a dimer composed of an α-subunit and a β-subunit linked together by hydrophobic and ionic interactions in a noncovalent manner. The β-subunit is common to hCG and other glycoprotein hormones, including luteinizing hormone (LH), follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH). The β subunit of hCG, in contrast, is unique and a separate independent molecule. During pregnancy, the placenta produces limited amounts of β-subunit and excess amount of α-subunit produced in pregnancy lead. The excess amounts of α-subunit lead to both hCG dimer production and the secretion of a free β-subunit. This excess α-subunit is then converted into a free α-subunit with an alternative structure. Free α-subunit is a glycoprotein hormone-processing intermediate with no known independent functions. It cannot combine with β-subunit. Free β-subunit has been shown to have a biological function separate from that of hCG. In cancer cells, the free β-subunit produced acts as an autocrine on the same cancer cells, promoting cell growth, invasion, and metastases. This chapter describes free α- and β-subunits structure, synthesis, and basic properties in detail.