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.
Highlights
In early pregnancy, human chorionic gonadotropin is produced primarily by differentiated syncytiotrophoblasts, and represents a key embryonic signal [1,2] essential for thre maintenance of pregnancy
HCG binds to its receptor to perform specialized roles in promoting angiogenesis in the uterine endothelium [4], maintaining myometrial quiescence [5], as well as fostering immunomodulation via alteration of activity of dendritic cells, the reduction of T-cell activation and cytokine production, promotion of T regulatory (Treg) cell recruitment, and an increase in proliferation of uterine natural killer (NK) cells at the maternal-fetal interface [6,7]
As a 237 amino acid heterodimer, human chorionic gonadotropin (hCG) is comprised of α-(93-amino acid, 14.5 kD) and β-(145-amino acid, 22.2 kD) subunits that are non-covalently linked by charge interactions and contain a total of eight carbohydrate side chains [11]
Summary
Human chorionic gonadotropin (hCG) is produced primarily by differentiated syncytiotrophoblasts, and represents a key embryonic signal [1,2] essential for thre maintenance of pregnancy. As a 237 amino acid heterodimer, hCG is comprised of α-(93-amino acid, 14.5 kD) and β-(145-amino acid, 22.2 kD) subunits that are non-covalently linked by charge interactions and contain a total of eight carbohydrate side chains [11]. It is a member of the glycoprotein hormone family that includes luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and follicle-stimulating hormone (FSH). As a result of its structural homogeneity to LH, hCG binds to luteinizing hormone/chorionic gonadotropin receptor (LHCGR) during the first 3–4 weeks of pregnancy, stimulating corpus luteal cells until the steroidogenic activity of the placenta produces sufficient progesterone to maintain pregnancy [14,15,16]. Expression of hCG genes is regulated by several hormones (corticosteroids, progesterone, GnRH), growth factors (placental growth hormone, leukemia inhibitory factor, vascular endothelial growth factor (VEGF)), cytokines (Interleukin (IL)-6, epidermal growth factors (EGF), tumor necrosis factor (TNF)-α), ligands of the nuclear receptor PPARγ and the homeobox gene (DLX3) [28,29,30,31]
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