# Human Chorionic Gonadotropin (hCG)

> Human chorionic gonadotropin (hCG) is a heterodimeric glycoprotein hormone produced by the placenta, built from an alpha and a beta subunit. Its best-known role is maintaining early pregnancy, and its measurement in blood and urine is a routine tool in obstetrics and gynecology. Research also covers its glycosylation variants, receptor signaling, immune effects and its use as a tumor marker.

Canonical: https://peptideproperties.com/compounds/hcg/

## Identity

- **Class:** Reproductive & HPG-Axis Compounds
- **Also known as:** Chorionic gonadotropin, hCG

## Key facts

- Class: glycoprotein hormone of the gonadotropin family; a heterodimer of alpha and beta subunits
- Origin: produced mainly by the placenta; essential for maintaining early pregnancy
- Shares its alpha subunit with LH, FSH and TSH; the beta subunit confers specificity
- Signals mainly through the LH/hCG receptor, the same receptor used by luteinizing hormone
- Circulates in multiple glycosylation forms, including hyperglycosylated hCG and free subunits
- No PubChem compound record; characterized as a biologic, not by a small-molecule formula
- Chorionic gonadotropin is an FDA-approved prescription biologic; prohibited in male athletes by WADA

## What Is Human Chorionic Gonadotropin (hCG)?

Human chorionic gonadotropin (hCG) is a glycoprotein hormone produced by the placenta and considered crucial for a healthy pregnancy. Its primary physiological function is to maintain early pregnancy.[1][2]Structurally, hCG is a heterodimeric glycoprotein composed of two subunits. A 2018 editorial introducing a journal special issue described it as both an endocrine regulator of gestation and a molecule relevant to cancer.[3]Measuring hCG in body fluids is one of the most commonly used tests in obstetrics and gynecology and is often among the first steps in evaluating female patients. A 2022 literature review noted that hCG is implicated in many processes beyond pregnancy, so test results can be misread, and that elevated hCG may point to other conditions, including malignancy. The same review covered hCG's origins, structure, pharmacokinetics, metabolism and therapeutic uses.[1]

## Chemical Structure and Molecular Identity

hCG is a heterodimeric glycoprotein composed of two subunits, alpha and beta, both carrying attached carbohydrate chains.[3] The alpha subunit, 92 amino acids long, is common to the glycoprotein hormone family, which also includes luteinizing hormone (LH), follicle-stimulating hormone (FSH) and thyroid-stimulating hormone (TSH). The 145-residue beta subunit gives hCG its distinct biological identity.PubChem has no compound record for hCG, so this page does not list a molecular formula, molecular weight or CAS number. As a glycosylated protein with variable sugar content, it is characterized by biologic standards rather than a single small-molecule identity.
### Glycoforms and fragments
hCG is not one uniform molecule. In biological fluids, intact hCG and its free alpha and beta subunits occur in multiple forms that differ mainly in glycosylation, and also in protein backbone modifications such as the urinary beta-core fragment of the beta subunit. These variants can be separated by isoelectric focusing. In a 1993 study using a panel of monoclonal antibodies against 17 hCG epitopes, every isoelectric variant of pregnancy-derived and tumor-derived hCG expressed the full set of epitopes, indicating that the carbohydrate differences were not of major antigenic relevance.[4]A distinct variant, hyperglycosylated hCG (hCG-H), carries additional carbohydrate. Reviews describe it as acting on the same tissues as standard hCG but through partly different signaling, including interaction with the TGF-beta receptor type II.[5]

## Research History and Development

Research on hCG has moved from viewing it as a single pregnancy hormone to treating it as a family of related molecules with endocrine, paracrine, diagnostic and immunological roles. A 2017 review described how discoveries over the preceding two decades shifted the emphasis from hCG as the hormone that sustains progesterone production by the corpus luteum to hCG as a powerful paracrine regulator of implantation and the dialogue between embryo and uterus.[5]Much of the work in the late 1980s and 1990s concerned measurement. Researchers developed monoclonal antibody immunoassays specific for intact hCG and for its free subunits, then used them to study variant forms in pregnancy and in tumors.[4][6]Receptor cross-reactivity was another early theme. Because hCG had been proposed as a thyroid stimulator, a 1994 study examined its binding to the recombinant human TSH receptor, comparing intact hCG with a desialylated variant, asialo-hCG.[7]More recent literature spans placental biology, maternal immune tolerance, environmental exposures, large population screening datasets and tumor pathology, reflecting the breadth summarized in the 2018 special issue on hCG in gestation and cancer.[3]

## Mechanisms Studied in Research

hCG acts mainly through the LH/hCG receptor, which it shares with luteinizing hormone, but studies show its downstream signaling and range of target tissues differ from those of LH. A 2017 review noted that differences in intracellular signaling between hCG and LH acting at the same receptor challenge the long-held view that the two hormones have identical effects.[5]
### Paracrine and vascular actions
The same review summarized paracrine actions attributed to hCG: controlling the fusion of trophoblast cells into syncytiotrophoblast, promoting angiogenesis through LH/hCG receptors on cells of the uterine spiral arteries and endometrial VEGF secretion, and preparing the endometrium for implantation. hCG has also been reported to interact with the TSH receptor.[5]That TSH receptor interaction appears weak for intact hCG. In thyroid carcinoma cells engineered to express the human TSH receptor, intact hCG inhibited TSH binding by no more than 20% at the highest concentration tested and did not raise cAMP. Asialo-hCG bound with much higher affinity and inhibited TSH-stimulated adenylate cyclase activity, behaving as an antagonist in this in-vitro system.[7]
### Immune regulation
In mouse cell experiments, hCG increased the frequency of regulatory T (Treg) cells through activation of the LH/CG receptor and, with involvement of IL-2, interfered with differentiation of CD4+ T cells into proinflammatory Th17 cells. Already-differentiated Th17 cells shifted toward an anti-inflammatory profile after hCG exposure.[8]
### Ovarian follicle signaling
In equine preovulatory follicles, mRNAs for the EGF-like factors epiregulin and amphiregulin rose in both granulosa and theca cells after hCG, peaking 33 to 39 hours later. In bovine follicles the induction was transient and limited to granulosa cells.[9]

## Key Findings From Published Studies

Published hCG research combines large human observational datasets, animal and cell studies, and tumor-pathology work, with most clinical evidence describing associations rather than causation.
### Human observational studies

- Pregnancy outcomes: a 2023 systematic review and meta-analysis found that second-trimester hCG at or above roughly 2 to 2.5 multiples of the median might be associated with preeclampsia (OR 2.08, 95% CI 1.26 to 3.44) and preterm delivery (OR 1.29, 95% CI 1.12 to 1.47), though the authors rated the evidence as very uncertain.[2]
- Fetal sex: in about 1.1 million California prenatal screening samples, hCG was higher in pregnancies with a female fetus by 11% in the first trimester and 8% in the second, with small fluctuations by maternal race, weight and age.[10]
- Phthalate exposure: in a birth cohort of 541 participants, certain urinary phthalate metabolites were associated with higher first-trimester hCG in women carrying female fetuses and lower hCG in those carrying males. An estimated 52% (MnBP) and 25% (MEHP) of the phthalate association with anogenital distance in males, and 78% (MBzP) in females, could be attributed to hCG.[11]
### Tumor marker research
In a 1992 study of serum from 749 cancer patients plus healthy and disease controls, low-level hCG elevations were common in all groups, but levels above 1000 pg/mL were highly diagnostic of gonadal tumors, specifically nonseminomatous testicular tumors. Free hCG beta subunit at or above 100 pg/mL appeared in 70% and 50% of nonseminomatous and seminomatous testicular cancers, 47% of bladder, 32% of pancreatic and 30% of cervical carcinomas, and in none of the controls.[6]In a 2023 immunohistochemistry study of 96 endometrial specimens, hCG positivity was 0% in normal endometrium, 8.3% in hyperplasia without atypia, 18.2% in atypical hyperplasia and 41.7% in endometrial cancer, leading the authors to propose hCG as a possible marker for these lesions.[12]
### Animal studies
In pregnant mice, hCG altered the expression of 720 genes in the myometrium and 3,348 in the cervix. It downregulated the contractility genes Gja1 and Oxtr while upregulating the prostaglandin-related genes Ptgfr and Ptgs2, findings the authors linked to hCG's previously reported ability to delay preterm labor in mice.[13] In a separate mouse study, transferring proinflammatory Th17 cells into pregnant mice caused fetal rejection and impaired spiral artery remodeling, effects partly avoided when the Th17 cells were first reprogrammed with hCG in vitro.[8]Because hCG circulates as intact hormone, free subunits and glycoforms, researchers typically verify preparations with batch-specific HPLC, mass spectrometry and bioactivity data.Because hCG circulates as intact hormone, free subunits and glycoforms, researchers typically verify preparations with batch-specific HPLC, mass spectrometry and bioactivity data.

## Regulatory and Research Status

Chorionic gonadotropin is an FDA-approved prescription drug, regulated in the United States as a biological product, and is also one of the most widely used diagnostic analytes in medicine. Approved forms include preparations purified from urine and a recombinant form, choriogonadotropin alfa. Its measurement in body fluids is a standard clinical test.[1]FDA-approved labeling for chorionic gonadotropin states that it has not been demonstrated to be effective as an adjunct for weight reduction. Over-the-counter products marketed as homeopathic hCG for weight loss are not FDA approved, and the FDA and FTC have issued warning letters to their sellers.In sport, chorionic gonadotropin is on the World Anti-Doping Agency Prohibited List for male athletes. Research use of hCG continues in reproductive biology, placental and immune research, and oncology, where its subunits and variants remain under study as tumor markers.[6][12]This page summarizes published research for reference purposes and does not provide guidance on human use.

## FAQ

**Is hCG a peptide or a protein?**
hCG is a glycoprotein, a protein with attached carbohydrate chains, rather than a short peptide. It is a heterodimer of an alpha subunit and a beta subunit. Because its sugar content varies, hCG circulates in several glycoforms, including hyperglycosylated hCG, and its free subunits and a urinary beta-core fragment are also found in biological fluids.

**Is hCG the same as LH?**
No. hCG and luteinizing hormone (LH) share the same alpha subunit and act on the same LH/hCG receptor, but their beta subunits differ. hCG is produced mainly by the placenta, while LH comes from the pituitary gland. Reviews note that hCG and LH trigger partly different intracellular signaling at the shared receptor, so their effects are not identical.

**How is hCG different from hMG?**
hCG is a single glycoprotein hormone produced by the placenta that acts mainly at the LH/hCG receptor. Menotropins, or human menopausal gonadotropin (hMG), is a preparation extracted from the urine of postmenopausal women that contains both FSH and LH activity. hCG therefore mimics LH-type signaling alone, while hMG supplies a mixture of two gonadotropins.

**Does hCG have a molecular formula or molecular weight on PubChem?**
No. PubChem has no compound record for hCG, so no official formula, molecular weight or CAS number is listed here. hCG is a large glycosylated protein whose carbohydrate content varies between molecules, which is why it is characterized by biologic standards such as immunoassay and bioactivity rather than a single small-molecule identity.

**Is hCG FDA approved?**
Yes. Chorionic gonadotropin is an FDA-approved prescription drug, available as urine-derived preparations and as a recombinant form, choriogonadotropin alfa. FDA-approved labeling states it has not been shown to be effective for weight reduction, and over-the-counter homeopathic hCG weight-loss products are not FDA approved. WADA prohibits hCG in male athletes.

**What does the research on hCG show?**
Published studies show hCG is essential for early pregnancy and acts through the LH/hCG receptor with paracrine effects on implantation, angiogenesis and immune tolerance. A meta-analysis linked high second-trimester hCG with preeclampsia and preterm delivery, with very uncertain evidence. Mouse studies report effects on Treg cells and uterine gene expression, and free hCG beta has been studied as a tumor marker.

**What is hyperglycosylated hCG?**
Hyperglycosylated hCG (hCG-H) is a variant of hCG with additional carbohydrate chains. Reviews describe it as acting on the same tissues as standard hCG but through partly different signaling, including interaction with the TGF-beta receptor type II, and assign it a key role in trophoblast invasion into the uterine lining during early pregnancy.

## References

1. Herkert D, Meljen V, Muasher L, et al. Human Chorionic Gonadotropin-A Review of the Literature. Obstetrical & gynecological survey 2022. PMID: 36136076
2. Skogler J, Moberg T, Tancredi L, et al. Association between human chorionic gonadotropin (hCG) levels and adverse pregnancy outcomes: A systematic review and meta-analysis. Pregnancy hypertension 2023. PMID: 37951184
3. Heidegger H, Jeschke U. Human Chorionic Gonadotropin (hCG)-An Endocrine, Regulator of Gestation and Cancer. International journal of molecular sciences 2018. PMID: 29772831
4. Berger P, Schwarz S, Spöttl G, et al. Variants of human chorionic gonadotropin from pregnant women and tumor patients recognized by monoclonal antibodies. The Journal of clinical endocrinology and metabolism 1993. PMID: 7688376
5. Borisova MA, Moiseenko DY, Smirnova OV. Human Chorionic Gonadotropin: Unknown about Known. Fiziologiia cheloveka 2017. PMID: 29509368
6. Marcillac I, Troalen F, Bidart JM, et al. Free human chorionic gonadotropin beta subunit in gonadal and nongonadal neoplasms. Cancer research 1992. PMID: 1377600
7. Hoermann R, Broecker M, Grossmann M, et al. Interaction of human chorionic gonadotropin (hCG) and asialo-hCG with recombinant human thyrotropin receptor. The Journal of clinical endocrinology and metabolism 1994. PMID: 8157724
8. Lentz LS, Stutz AJ, Meyer N, et al. Human chorionic gonadotropin promotes murine Treg cells and restricts pregnancy-harmful proinflammatory Th17 responses. Frontiers in immunology 2022. PMID: 36203576
9. Sayasith K, Lussier J, Doré M, et al. Human chorionic gonadotropin-dependent up-regulation of epiregulin and amphiregulin in equine and bovine follicles during the ovulatory process. General and comparative endocrinology 2013. PMID: 23178756
10. Adibi JJ, Lee MK, Saha S, et al. Fetal sex differences in human chorionic gonadotropin fluctuate by maternal race, age, weight and by gestational age. Journal of developmental origins of health and disease 2015. PMID: 26242396
11. Adibi JJ, Lee MK, Naimi AI, et al. Human Chorionic Gonadotropin Partially Mediates Phthalate Association With Male and Female Anogenital Distance. The Journal of clinical endocrinology and metabolism 2015. PMID: 26200238
12. Daggez M, Dolanbay M, Akgun H, et al. Human chorionic gonadotropin expression in endometrial hyperplasia and endometrial carcinoma: could it be a new marker? International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 2023. PMID: 37001896
13. Motomura K, Romero R, Galaz J, et al. Human Chorionic Gonadotropin Modulates the Transcriptome of the Myometrium and Cervix in Late Gestation. Reproductive sciences (Thousand Oaks, Calif.) 2021. PMID: 33650091