hCG: Biological Functions and Clinical Applications

Abstract

Human chorionic gonadotropin (hCG) is produced primarily by differentiated syncytiotrophoblasts, and represents a key embryonic signal that is essential for the maintenance of pregnancy. hCG can activate various signaling cascades including mothers against decapentaplegic homolog 2 (Smad2), protein kinase C (PKC), and/or protein kinase A (PKA) in several cells types by binding to luteinizing hormone/chorionic gonadotropin receptor (LHCGR) or potentially by direct/indirect interaction with transforming growth factor beta receptor (TGFβR). The molecule displays specialized roles in promoting angiogenesis in the uterine endothelium, maintaining myometrial quiescence, as well as fostering immunomodulation at the maternal-fetal interface. It is a member of the glycoprotein hormone family that includes luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and follicle-stimulating hormone (FSH). The α-subunit of hCG displays homologies with TSH, LH, and FSH, whereas the β subunit is 80-85% homologous to LH. The hCG molecule is produced by a variety of organs, exists in various forms, exerts vital biological functions, and has various clinical roles ranging from diagnosis and monitoring of pregnancy and pregnancy-related disorders to cancer surveillance. This review presents a detailed examination of hCG and its various clinical applications.

Keywords: clinical applications; human chorionic gonadotropin (hCG); luteinizing hormone/chorionic gonadotropin receptor (LHCGR); pregnancy; trophoblasts; α and β hCG subunits.

Figure 1

Cellular sources, targets, associated signaling cascades, and functions of various hCG isoforms in non-pregnant and pregnant women. LHCGR: luteinizing hormone/choriogonadotropin receptor; TGFβR: transforming growth factor beta receptor; ?: hCG may bind to relevant receptor in target cells; Smad2: similar to drosophila gene ‘mothers against decapentaplegic’ 2; Gq: heterotrimeric G protein subunit that activates phospholipase C (PLC)-associated protein kinase C (PKC); Gs: heterotrimeric G protein subunit that activates cAMP-dependent protein kinase A (PKA) signaling by activating adenylyl cyclase; hCH-S: sulfated hCG; hCG-H: hyperglycosylated hCG.