HCG — Peptide Protocol Wiki reference

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Start the 7-step beginner guide Peptides Side Effects New Directory Learn Tools Blog News About HCG 📋 Overview 🧬 Molecule 🔄 Similar ⚠️ Side Effects 💉 Dosing 🔬 Research 🚨 Risks 👥 Community 📊 Community Data Home Peptides HCG Reproductive Health Hormonal Health approved HCG Also known as: Human Chorionic Gonadotropin, hCG, Pregnyl, Novarel, Ovidrel Compare with 1 peptide Research compiled by Peptide Protocol Wiki 📅 Updated February 1, 2026 Citations Verified TL;DR HCG (Human Chorionic Gonadotropin) is a glycoprotein hormone composed of alpha and beta subunits.

It mimics luteinizing hormone (LH) activity and is FDA-approved for treatment of hypogonadism, cryptorchidism, and as part of assisted reproductive technology protocols.

Browse all reproductive peptides → Table of Contents 📌 TL;DR • FDA-approved for multiple reproductive indications • Stimulates testicular testosterone production in males • Triggers ovulation in fertility treatment protocols • Maintains Leydig cell function during testosterone therapy Community-Reported Side Effects Anecdotal ?

support, and ovulation induction 💉 Dosing Amount 250-500 IU per injection (TRT adjunct); 1500-5000 IU (fertility protocols) Frequency Every other day or 2-3 times per week Duration Ongoing while on TRT; or 6-12 weeks for PCT/fertility protocols 💊 Administration Route SC Schedule Every other day or 2-3 times per week Timing No specific time of day; maintain consistent schedule ✓ Rotate injection sites 📅 Cycle Duration Ongoing while on TRT; or 6-12 weeks for PCT/fertility protocols Repeatable Yes Preparation & Storage Diluent: Bacteriostatic water ⚗️ Suggested Bloodwork ( 6 tests) Total and free testosterone When: Baseline Why: Baseline androgen status Estradiol (sensitive assay) When: Baseline Why: HCG increases intratesticular aromatization LH and FSH When: Baseline Why: Baseline gonadotropin levels CBC When: Baseline Why: Baseline hematology (HCG can increase erythropoiesis) Semen analysis (if fertility goal) When: Baseline Why: Baseline fertility assessment Estradiol When: 4-6 weeks Why: HCG can significantly raise estradiol; may need AI if elevated 💡 Key Considerations → IM injection yields higher Cmax and AUC than SC, especially in obese individuals → Higher doses (1500-5000 IU) are used for fertility induction combined with FSH/HMG but increase estradiol conversion → Contraindication: Contraindicated in androgen-dependent neoplasms (prostate cancer), precocious puberty, and pregnancy Subscribe to unlock this conte

PLC–IP3/DAG–Ca2+ signaling • LHCGR couples to Gq/11, activating PLC to produce IP3 and DAG, mobilizing Ca2+ and activating PKC.

Ca2+/calmodulin-dependent kinases facilitate cholesterol transport and acute steroidogenesis, and PKC can feed into ERK signaling.

Restore access No thanks, continue reading Related Reading Peptide Gonadorelin GnRH hypothalamic peptide Peptide HMG human menopausal gonadotropin Peptide Kisspeptin reproductive hormone peptide How HCG works at the cellular level Overview of HCG benefits and applications Scientific Details Molecular Formula Glycoprotein heterodimer (~25.7 kDa peptide + ~10-15 kDa glycans) Molecular Weight 36700 Da CAS Number 9002-61-3 Sequence Heterodimer: alpha subunit (92 aa) + beta subunit (145 aa), 237 aa total What is HCG?

Mechanism of Action # Human chorionic gonadotropin (hCG) is a heterodimeric glycoprotein hormone that binds and activates the luteinizing hormone/chorionic gonadotropin receptor (LHCGR), a class A GPCR expressed in gonadal and reproductive tissues.

High-resolution structures show hCG engages the large extracellular domain (ECD) and activates the transmembrane core via a hinge “push–pull” mechanism in which a conserved hinge loop fragment (P10) functions as a tethered agonist, stabilizing an active 7TM conformation that couples to G proteins and β-arrestins (simoniUnknownyearoggettoendocrinereview

Ligand-specific contacts at the ECD/hinge and hormone glycosylation underlie biased signaling differences between hCG and LH (casariniUnknownyearadvancearticle pages 17-18).

Canonical Gs–cAMP–PKA signaling and steroidogenesis • LHCGR–Gs activates adenylyl cyclase, elevating cAMP and activating PKA.

PKA phosphorylates CREB and promotes transcription of steroidogenic genes, notably STARD1 (StAR) and CYP enzymes including CYP11A1, coordinating cholesterol transfer to mitochondria and conversion to pregnenolone; StAR phosphorylation and expression are integral to the acute steroidogenic response.

β-arrestin recruitment, receptor trafficking, and endosomal signaling • Agonist-occupied LHCGR is phosphorylated by GRKs, recruits β-arrestins, and internalizes.

β-arrestins scaffold MAPK components to generate a delayed ERK1/2 wave and associate with PDEs to modulate cAMP microdomains.

Internalized LHCGR can remain signaling-competent in endosomes, forming complexes with G proteins and β-arrestins that sustain cAMP (regulated by APPL1) (simoniUnknownyearoggettoendocrinereviewsproposal pages 20-22).

In a retrospective cohort of ovarian tumors, serum hCG was positive in 67% of malignant versus 26.7% of benign cases, and tumor tissue expressed hCG in 68%.

or aggregation/internalization, and sustained cAMP, supporting ligand-biased outcomes (casariniUnknownyearadvancearticle pages 20-21, simoniUnknownyearoggettoendocrinereviewsproposal pages 20-22).

ERK/MAPK and PI3K/AKT pathways • LHCGR activation also engages ERK/MAPK and PI3K/AKT.

ERK and AKT contribute to survival, differentiation, and are required, together with PKA, for full STARD1 expression in several contexts (simoniUnknownyearoggettoendocrinereviewsproposal pages 20-22).

In primary human granulosa cells, LH elicits stronger and more sustained ERK1/2 and AKT phosphorylation than hCG at equipotent doses, consistent with a proliferative/survival bias of LH versus a steroidogenic bias of hCG.

Angiogenic signaling and molecular targets • hCG promotes angiogenesis in the corpus luteum and placenta through multiple pathways.

It directly induces endocrine gland–derived VEGF (EG‑VEGF/prokineticin‑1) and its receptors (PROKR1/2) via LHCGR → cAMP/PKA acting on CRE elements in the EG‑VEGF promoter, increasing EG‑VEGF expression and secretion in first‑trimester placental tissues.

hCG also increases VEGF expression and angiogenic activity, including endothelial/pericyte responses, with evidence for VEGF upregulation via NF‑κB signaling in luteal cells.

Hyperglycosylated hCG (hCG‑H) is strongly pro‑angiogenic and can act through TGFβRII independently of LHCGR, broadening angiogenic control beyond classical GPCR signaling.

Endometrial and immunomodulatory actions • At the endometrial interface, hCG increases leukemia inhibitory factor (LIF) and decreases interleukin‑6 (IL‑6) in epithelial cells, fosters stromal decidualization, and induces EGF‑family ligands (e.g., amphiregulin), which coordinate receptivity and luteal support.

hCG modulates immune tolerance by attracting and expanding regulatory T cells, altering T‑cell activation markers and cytokines, and by acting on uterine NK cells via a mannose receptor (which lacks LHCGR) to regulate their proliferation.

These pleiotropic actions integrate with LHCGR‑dependent cAMP/kinase signaling to promote implantation and

Mechanistic distinction from LH (biased agonism at LHCGR) • Although hCG and LH share LHCGR, they stabilize distinct receptor conformations and produce different signaling ensembles.

Relative to LH, hCG is more potent for cAMP and often produces stronger CREB/CRE‑dependent steroidogenic transcription and sustained progesterone, whereas LH tends to favor ERK/AKT activation, proliferation/survival signals, and distinct gene regulation (e.g., NRG1 inhibition, CYP19A1 control) under equipotent conditions.

hCG also more readily engages β‑arrestin2 and Gq/Ca2+ and promotes receptor aggregation/endosomal signaling (casariniUnknownyearadvancearticle pages 20-21, simoniUnknownyearoggettoendocrinereviewsproposal pages 20-22).

In reproductive tissues, hCG additionally regulates angiogenic factors (EG‑VEGF, VEGF) and endometrial/immune mediators (LIF, IL‑6, Treg/uNK/complement), thereby coordinating luteal maintenance, implantation, and placentation.

hCG Mechanism of Action summary table: Component Mechanism / Pathway Key Molecular Events Representative Outputs Notes on hCG vs LH Receptor binding /

Receptor active state, G protein recruitment, possible dimer/oligomer formation hCG structural features (CTP, glycosylation) and ECD contacts bias receptor conformation and signaling vs LH (simoniUnknownyearoggettoendocrinerevi...

Regulators and professional societies state HCG is not proven effective for obesity and do not endorse its use for weight loss.

Increased steroidogenesis (pregnenolone → progesterone/testosterone), progesterone secretion hCG ~5× more potent for cAMP generation; slower kinetics (sustained cAMP) → stronger steroidogenic drive in many models vs LH β-arrestin recruitment / endosomal signaling GRK phosphorylation → β-arrestin binds → receptor desensitization, scaffolding of MAPKs, clathrin-mediated internalization; endosomal signalosomes ...

β-arrestin scaffolds Src/ERK modules; PDE/β-arrestin interactions modulate cAMP; internalized LHCGR complexes can produce persistent/compartmentali...

ceptor aggregation/internalization than LH, contributing to signaling bias and sustained res...

ERK/MAPK and PI3K → AKT G protein- and β-arrestin-dependent activation of Ras/Raf/MEK/ERK and Gβγ→PI3K→AKT pathways ERK and AKT phosphorylation regulate transcription factors and post-translational modification of steroidogenic machinery (StAR expression), promot...

Cell proliferation/survival (anti‑apoptotic signals), modulation of steroidogenic gene expression (StAR, aromatase regulation) LH tends to elicit stronger ERK/AKT activation in granulosa cells, whereas hCG is more steroidogenic via cAMP; both pathways necessary for full StA...