HCG (Human Chorionic Gonadotropin)

HCG (Human Chorionic Gonadotropin) is a glycoprotein hormone produced by placental syncytiotrophoblasts during pregnancy, where it maintains corpus luteum progesterone production through the first trimester by sustaining LHCGR (LH/hCG receptor) stimulation after the pituitary LH surge that triggered ovulation. In research, HCG serves as the standard LHCGR agonist for studies of Leydig cell steroidogenesis, gonadal biology, and HPG axis pharmacology — preferred over native LH because HCG's dramatically extended half-life (24-36 hours versus LH's 20-30 minutes) enables sustained LHCGR stimulation without continuous dosing.

HCG is a non-covalent heterodimeric glycoprotein consisting of an alpha subunit (92 amino acids, identical to the alpha subunits of LH, FSH, and TSH) and a unique HCG beta subunit (145 amino acids). The HCG beta subunit shares approximately 82% sequence identity with the LH beta subunit but contains a C-terminal peptide (CTP) extension of approximately 30 amino acids absent from LH beta. This CTP carries four O-linked oligosaccharide chains heavily sialylated with N-acetylneuraminic acid residues. The sialic acid groups are responsible for HCG's extended half-life: they prevent asialoglycoprotein receptor-mediated hepatic clearance (which would rapidly remove desialylated glycoproteins) and sterically impede renal filtration, producing the approximately 24-36 hour plasma half-life that enables corpus luteum maintenance throughout the first trimester without continuous pituitary LH secretion.

LHCGR is a Gs-coupled class A GPCR with the unique property of having an unusually large N-terminal leucine-rich repeat extracellular domain (ECD) that spans approximately 330 amino acids and provides the primary binding interface for both LH and HCG. HCG binds LHCGR with approximately 2-3 fold higher affinity than LH, partially attributable to the HCG CTP interacting with the LHCGR ECD in addition to the conserved glycoprotein hormone binding interactions. LHCGR Gs coupling raises cAMP via adenylyl cyclase, activating PKA. PKA phosphorylates StAR (Steroidogenic Acute Regulatory protein) at Ser194 — the rate-limiting step for cholesterol transport across the inner mitochondrial membrane — and drives transcription of the complete steroidogenic enzyme cascade: CYP11A1 (cholesterol→pregnenolone), CYP17A1 (pregnenolone→DHEA), HSD3B2 (DHEA→androstenedione), and HSD17B3 (androstenedione→testosterone).

Leydig cells exhibit approximately 99% spare receptor capacity for testosterone production — maximal steroidogenesis occurs when only approximately 1% of total LHCGR is occupied. This receptor reserve has important research implications: LHCGR downregulation of up to 99% can occur without immediate reduction in testosterone output, and concentration-response curves for LHCGR occupation (measured by radioligand binding) do not parallel dose-response curves for testosterone production (measured by RIA or LC-MS/MS).

Research applications include: Leydig cell steroidogenic cascade studies (testosterone, progesterone, and pathway intermediates by RIA or LC-MS/MS); LHCGR binding kinetics (radioligand displacement assays with [125I]-hCG); comparison with LH for half-life and receptor occupancy duration effects on steroidogenesis kinetics; HPG axis research combining Kisspeptin-10 (GPR54 agonist), Gonadorelin (GnRHR agonist), and HCG (LHCGR agonist) for complete axis characterisation; and corpus luteum biology in granulosa cell models.

Supplied in IU (International Units). Reconstitute in bacteriostatic water per vial instructions. Store lyophilised at -20°C. For laboratory and analytical research purposes only.

For Leydig cell research: primary murine or rat Leydig cells isolated from testicular interstitium provide the most physiologically authentic LHCGR research model. MA-10 (mouse Leydig tumour cells) and MLTC-1 cells are established immortalised Leydig models expressing functional LHCGR. Key endpoint: testosterone production measured by competitive ELISA or LC-MS/MS in conditioned medium after 2-24 hours of HCG stimulation. LH positive control at matched molar concentration (adjust for MW difference — HCG approximately 36,700 vs LH approximately 28,000 g/mol) allows direct half-life and potency comparison. Supplied in IU. Reconstitute in bacteriostatic water per vial instructions. Store lyophilised at -20°C. For laboratory and analytical research purposes only.