HCG (Chorionic Gonadotropin)

Technical data

INN name

Human Chorionic Gonadotropin

CAS

9002-61-3

Molecular formula

C₁₄₈₈H₂₃₀₉N₃₈₁O₄₅₉S₁₇

Molecular weight

36700 g/mol

Identity and composition

La HCG (Human Chorionic Gonadotropin) is a heterodimeric hormonal glycoprotein used as a reference material in research on steroidogenesis and LH receptor signaling. It is studied mainly for its ability to stimulate intratesticular testosterone synthesis and the activity of Leydig and granulosa cells.

As for its chemical identity, HCG has number CAS 9002-61-3 and a molecular mass of ~36.7 kDa (approximately 14.5 kDa of the alpha subunit plus 22.2 kDa of the beta subunit). Structurally it is a heterodimer of 237 amino acids, formed by an alpha subunit (92 amino acids, common to LH, FSH, and TSH) and a specific beta subunit (145 amino acids). As it is a heterodimeric glycoprotein, a fixed molecular formula does not apply and a single primary sequence is not included; both fields are described only by composition.

Frequent synonyms: hCG, Human Chorionic Gonadotropin, human chorionic gonadotropin, Choriogonadotropin, CG.

Product for research use.

Mechanism of action

HCG acts as agonist of the LH/choriogonadotropin receptor (LHCGR) present in the membrane of Leydig and granulosa cells. Its binding to the LHCGR activates the protein Gαs, which stimulates the pathway cAMP/PKA and the phosphorylation of CREB, triggering steroidogenesis: synthesis of testosterone in the Leydig cells and of steroids in the granulosa (PMC5217336).

The molecule is a heterodimer whose alpha subunit is identical to that of LH, while the specific beta subunit confers selectivity on it. In in vitro models with murine Leydig cells, HCG has been observed to be approximately 10 times more potent than LH in cAMP recruitment (EC50 ~18.6 pM versus ~192 pM for LH), although downstream testosterone synthesis is equivalent between the two (PMC5217336). The glycosylation of HCG increases its activity on the receptor and slows its metabolism relative to LH. There has also been described a biased agonism biased agonism between LH and HCG on the LHCGR: a quantitatively distinct but qualitatively similar activation of the early signaling pathways.

Pharmacokinetics

The reviewed literature reports for HCG a plasma half-life of approximately 36 hours, compared to around 30 minutes for LH (PMC6087849). The glycosylated side chain of hCG slows its metabolism, which allows sustained and prolonged stimulation of steroidogenesis and, in a research context, less frequent dosing. These parameters come from clinical review and should be interpreted as a reference, not as a prediction of behavior in a specific protocol.

Scientific evidence

HCG is an established hormonal compound with documented clinical and research use. The evidence reviewed here corresponds to mechanistic in vitro studies and clinical reviews, not to phase-specific trials for new indications.

In basic research, its signaling mechanism via LHCGR in Leydig cells has been characterized (PMC5217336), and in the clinical setting its role in the infertility of men with hypogonadism has been reviewed, where it has been described as an alternative or adjunct to testosterone replacement therapy (PMC6087849). Preliminary evidence suggests a role in the stimulation of intratesticular testosterone, but the detail of clinical trial phases (NCT) for new indications was not confirmed in the open sources. Interpret the scope with caution.

Research applications

Ideal for (research use):

• In vitro mechanistic studies of LHCGR receptor signaling (Gαs/cAMP/PKA/CREB pathways) in Leydig and granulosa cells.
• Research on steroidogenesis and intratesticular testosterone synthesis.
• Comparative studies of potency and pharmacodynamics versus LH.
• Models of follicular stimulation and steroidogenesis in reproductive research.

Not applicable for:

• clinical use, diagnosis, or treatment. Product for research use.
• Any therapeutic, dietary, or self-medication use outside a controlled research environment.

Research protocols

The reviewed sources describe the use of HCG in mechanistic and clinical-review contexts, but did not provide a validated numerical dosing scheme that can be reproduced here. For that reason no specific doses are included. What is qualitatively documented is that its prolonged half-life (~36 h) allows, in research, sustained stimulation of steroidogenesis with less frequent administration than LH (PMC6087849). Any parameter of concentration, frequency, or route must be defined according to the experimental design and the corresponding primary references.

Reconstitution

HCG is usually presented in the form lyophilized (powder). As a standard general laboratory guideline, it is reconstituted with bacteriostatic water (sterile water with approximately 0.9% benzyl alcohol as a preservative), added slowly down the wall of the vial to avoid abrupt agitation of the glycoprotein.

• Direct the diluent against the wall, not directly onto the pellet.
• Do not shake vigorously; swirl the vial gently until complete dissolution.
• Calculate the final concentration according to the diluent volume used and the vial content (2000 IU, 5000 IU or 10000 IU).

Handle with aseptic technique. For research use only.

Stability and storage

As standard laboratory handling guidance:

• Lyophilized (unreconstituted): is the most stable form; it is stored refrigerated and, for prolonged storage, frozen, protected from light and humidity.
• Reconstituted: keep refrigerated and use within a short period; for longer-term preservation it is usually divided into aliquots and frozen to avoid repeated freeze-thaw cycles, which degrade the glycoproteins.

Avoid mechanical agitation and high temperatures. These ranges are general handling guidance, not validated specifications of a particular batch.

Safety profile

The safety profile available in the reviewed sources is limited. A clinical review on infertility in men with hypogonadism describes HCG as a safe and effective alternative or adjuvant to testosterone replacement therapy, without detailing significant adverse events in the open sources (PMC6087849).

It should be emphasized that the consulted sources did not provide an exhaustive safety profile: no data on ovarian hyperstimulation syndrome or on other adverse events were confirmed, nor formal contraindications. For this reason, these notes must be interpreted with caution and do not substitute a complete toxicological evaluation. Product for research use.

Comparative context

Compared with the LH (luteinizing hormone), with which it shares the alpha subunit and the same LHCGR receptor, HCG presents relevant differences:

• Potency: in in vitro models, HCG is approximately 10 times more potent than LH in cAMP recruitment (EC50 ~18.6 pM vs ~192 pM), although the final downstream synthesis of testosterone is equivalent between the two (PMC5217336).
• Half-life: HCG has a much longer half-life (~36 h) than LH (~30 min), thanks to its glycosylation, which slows metabolism (PMC6087849).
• Signaling: biased agonism has been described between the two on the LHCGR, with quantitatively distinct but qualitatively similar activation of the early pathways.

In summary: greater initial potency and longer-lasting action than LH, with a comparable final steroidogenic outcome.

History and development

HCG is a endogenous glycoprotein hormone of placental origin, well characterized in the hormonal literature and with CAS number 9002-61-3. Its heterodimeric structure—an alpha subunit common to LH, FSH, and TSH, plus a specific beta subunit—places it within the family of the gonadotropins.

Its relevance in research derives from its affinity for the LHCGR receptor and from its prolonged half-life, properties that have made it a tool for the study of steroidogenesis and an object of clinical reviews on male fertility and ovulation induction (PMC5217336; PMC6087849). The open sources reviewed focus on its mechanism and its clinical context rather than on a detailed chronology of its development.

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Scientific references (6)

Peer-reviewed literature on HCG (Chorionic Gonadotropin), with its PubMed identifier when available:

• Human Chorionic Gonadotropin (Betz D et al. · 2026) PMID 30422545.
• Human Chorionic Gonadotropin-Mediated Immune Responses That Facilitate Embryo Implantation and Placentation (Schumacher A et al. · Frontiers in immunology · 2019) PMID 31921157.
• Human Chorionic Gonadotropin and Breast Cancer (Schüler-Toprak S et al. · International journal of molecular sciences · 2017) PMID 28754015.
• Human chorionic gonadotropin treatment: a viable option for management of secondary hypogonadism and male infertility (Fink, et al. · Expert Review of Endocrinology & Metabolism · 2021) PMID 33345656.
• Human Chorionic Gonadotropin monotherapy for the treatment of hypogonadal symptoms in men with total testosterone > 300 ng/dL (Madhusoodanan, et al. · International Braz J Urol · 2019) PMID 31408289.
• Indications for the use of human chorionic gonadotropic hormone for the management of infertility in hypogonadal men (Lee, et al. · Translational Andrology and Urology · 2018) PMID 30159241.

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