Description

Human Chorionic Gonadotropin (hCG) – Advanced Biochemical Mechanism Profile

(Glycoprotein hormone; LH receptor agonist)

Human chorionic gonadotropin is a heterodimeric glycoprotein composed of α- and β-subunits, structurally homologous to luteinizing hormone (LH). Its biological activity is mediated through selective activation of the Luteinizing Hormone/Choriogonadotropin Receptor (LHCGR), a Gs-coupled Class A GPCR.

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✅ 1. Receptor Target: LHCGR

Receptor: Luteinizing Hormone / Chorionic Gonadotropin Receptor
Receptor Class: GPCR (G-protein–coupled receptor)
Primary Signal: Gs → Adenylate Cyclase → ↑ cAMP → PKA activation

hCG binds the extracellular N-terminal domain of LHCGR, producing:

• Elevated cAMP

• PKA-dependent phosphorylation

• Activation of CREB transcriptional pathways

• ↑ StAR protein function and cholesterol transport into mitochondria

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✅ 2. Core Intracellular Signaling Cascades

A. cAMP/PKA/CREB Pathway (Primary Mechanism)

1. hCG → LHCGR → Gs protein

2. Adenylate Cyclase activated

3. ↑ intracellular cAMP

4. PKA phosphorylates:

   • StAR (Steroidogenic Acute Regulatory protein)

   • Cholesterol side-chain cleavage enzyme (CYP11A1)

5. CREB translocates to nucleus → binds CRE promoter regions

Gene targets commonly monitored:

• STAR

• CYP11A1

• HSD3B1

• CYP17A1

• LHR (LHCGR upregulation)

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B. PI3K / Akt Pathway

hCG stimulation can activate:

• PI3K → Akt phosphorylation

• Inhibition of pro-apoptotic FOXO transcription factors

• Regulation of steroidogenic cell survival and mitochondrial integrity

Associated gene readouts:

• BCL2

• MCL1

• SOD2 (antioxidant response)

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C. ERK1/2 MAPK Pathway

Secondary signaling through:

• Ras → Raf → MEK1/2 → ERK1/2

• Supports gene expression for steroidogenesis and cellular proliferation

• Used as a research marker for gonadotropin-responsive metabolic pathways

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✅ 3. Steroidogenic Enzymes Influenced in Research Models

hCG increases transcription and/or activity of:

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✅ 4. Second Messengers & Molecular Outputs

• ↑ cAMP

• ↑ PKA

• ↑ CREB phosphorylation

• ↑ Ca²⁺ influx in steroidogenic cells

• Mitochondrial cholesterol import (StAR-mediated)

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✅ 5. Gene-Level Summary (Frequently Measured in Studies)

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Research-Only Use Classification

Human chorionic gonadotropin is provided solely for in-vitro laboratory research.
It is not approved for ingestion, injection, consumption, or any diagnostic or therapeutic application in humans or animals.