Background
Trophoblast cells maintain the corpus luteum during early development by secreting human chorionic gonadotropin (hCG), which promotes the synthesis and secretion of progesterone, thus providing the necessary environment for embryo implantation and early development. A variety of embryo-protective effects have been attributed to hCG, a glycoprotein hormone with varying degrees of glycosylation, consisting of two subunits (α and β) linked by a non-covalent bond, which can be classified into four isoforms, namely, classical hCG, hyperglycosylated hCG, free β-subunit, and hCG sulfate, which have different physiological functions.
Figure 1. Structure of hCG
(Source: d'Hauterive SP, et al. 2022)
Classical hCG plays an important role in synchronizing the development of the fetus and the endometrium, and is the earliest molecule secreted by the embryo, with its RNA being transcribed at the eight-cell stage and produced before the blastocyst is implanted. During implantation, hCG is secreted mainly by syncytiotrophoblasts and can be detected clinically in maternal blood up to 10 days after ovulation. hCG concentration peaks around the 10th and 11th weeks of gestation, after which the expression decreases and remains at a basal level from the 12th week of gestation until the end of pregnancy. The concentration of hCG is significantly higher throughout the process than in non-pregnant women, and is also a marker of placental function. Highly glycosylated hCG (hCG-H) has two additional oligosaccharide-linked Os on the β-subunit compared to the classical hCG molecule, and is mainly produced by extrachorionic trophoblast cells. It is produced in large quantities during the first trimester of pregnancy, decreases rapidly thereafter, and disappears completely from the maternal bloodstream by the end of the first trimester, and can therefore be used to predict the outcome of pregnancies in women suspected of miscarrying early in the pregnancy. Acting through autocrine secretion, hCG-H reduces trophoblast apoptosis and induces embryo implantation and trophoblast infiltration. Monitoring hCG-H also predicts treatment response in Down syndrome, preeclampsia, and trophoblastic diseases.
hCG free β subunit is an agonist of LH-hCG receptor (LHCGR) and an antagonist of TGF-β receptor, and its abnormal elevation can predict hypertension in pregnancy. Some researchers have found that there is a statistically significant correlation between the level of circulating free β subunit and markers of inflammation and oxidative stress in patients with perinatal pregnancy hypertension. In addition the free β subunit has been found to promote the development of a number of cancers such as germ cell malignancies, sarcomas, teratomas and lymphomas. hCG sulfate, an isomer of hCG, is produced by the pituitary gland in nonpregnant women and is secreted at the same time as LH during the menstrual cycle. Despite its low concentration, it is 50 times more potent than LH, stimulating androstenedione production during the follicular phase, as well as stimulating ovulation and corpus luteum formation. It also helps to stimulate progesterone production during the luteal phase.
Alternative Names
Anti-human chorionic gonadotropin beta monoclonal antibody
Anti-human chorionic gonadotropin β monoclonal antibody
Anti-hCG β monoclonal antibody
References
- 1. d'Hauterive SP, et al. Human Chorionic Gonadotropin and Early Embryogenesis: Review. Int J Mol Sci. 2022 Jan 26;23(3):1380.
- 2. Schumacher A, et al. Human Chorionic Gonadotropin-Mediated Immune Responses That Facilitate Embryo Implantation and Placentation. Front Immunol. 2019 Dec 10;10:2896.
References
Globin-mediated nitric oxide detoxification in the foodborne pathogenic bacterium Campylobacter jejuni proceeds via a dioxygenase or denitrosylase mechanism
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
Authors: Shepherd, Mark; Bernhardt, Paul V.; Poole, Robert K.
Abstract
Nitric oxide (NO(center dot)) is a toxin, but bacteria have evolved various strategies to detoxify this harmful radical to nitrate, the best known mechanism being the dioxygenase reaction of bacterial flavohaemoglobins. In addition, globins can form oxoferryl (Fe(IV)=O) species through the reaction of the ferric haem with hydrogen peroxide: these species can also detoxify NO(center dot) to nitrite and nitrate. During infection, Compylo-bacter is exposed to both NO(center dot) and hydrogen peroxide. A question therefore arises: does Campylobacter jejuni utilize its single domain globin (Cgb) to detoxify NO(center dot) via the oxoferryl route, or via the more conventional dioxygenase or denitroxylase routes? The data herein demonstrate that the reaction between Cgb and hydrogen peroxide is much slower than for other globins, and subsequent reaction between the oxoferryl species and NO(center dot) is unfavourable. Furthermore, NO(center dot) may bind to Cgb in the oxyferrous, ferrous and ferric states. The ample opportunity for NO(center dot) to interact with ferrous and ferric Cgb, and the unfavourable reaction of ferric Cgb with hydrogen peroxide, suggests that NO(center dot) detoxification in C. jejuni proceeds via a dioxygenase or denitroxylase route requiring the haem iron to exist only in the Fe(II) or Fe(III) redox states. (C) 2011 Elsevier Inc. All rights reserved.
Reversible hexa- to penta-coordination of the heme Fe atom modulates ligand binding properties of neuroglobin and cytoglobin
IUBMB LIFE
Authors: Pesce, A; De Sanctis, D; Nardini, M; Dewilde, S; Moens, L; Hankeln, T; Burmester, T; Ascenzi, P; Bolognesi, M
Abstract
Neuroglobin (Ngb) and cytoglobin (Cygb) are two recently discovered intracellular members of the vertebrate hemoglobin (Hb) family. Ngb, predominantly expressed in nerve cells, is of ancient evolutionary origin and is homologous to nerve-globins of invertebrates. Cygb, present in many different tissues, shares common ancestry with myoglobin (Mb) and can be traced to early vertebrate evolution. Ngb is held to facilitate O-2 diffusion to the mitochondria and to protect neuronal cells from hypoxic-ischemic insults, may be an oxidative stress-responsive sensor protein for signal transduction, and may carry out enzymatic activities, such as NO/O-2 scavenging. Cygb is linked to collagen synthesis, may provide O-2 for enzymatic reactions, and may be involved in a ROS (NO)-signaling pathway(s). Ngb and Cgb display the classical three-over-three alpha-helical fold of Hb and Mb, and are endowed with a hexa-coordinate heme-Fe atom, in their ferrous and ferric forms, having the heme distal HisE7 residue as the endogenous ligand. Reversible hexa- to penta-coordination of the heme Fe atom modulates ligand binding properties of Ngb and Cygb. Moreover, Ngb and Cygb display a tunnel/cavity system within the protein matrix held to facilitate ligand channeling to/from the heme, multiple ligand copies storage, multi-ligand reactions, and conformational transitions supporting ligand binding.
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