HCG

Human chorionic gonadotropin (hCG) is a glycoprotein hormone produced by syncytiotrophoblast cells of the placenta during pregnancy. It is an FDA-approved pharmaceutical available as Pregnyl and Novarel (powder for reconstitution, IM/SC injection) and as Ovidrel (subcutaneous injection of recombinant choriogonadotropin alfa). It is approved for treatment of hypogonadotropic hypogonadism in males, cryptorchidism in prepubertal males, and ovulation induction in females.

hCG is technically not a peptide — it is a glycoprotein heterodimer with a molecular weight of approximately 36,700 Da (protein backbone; full glycosylated form is ~37,000–38,000 Da). It is conventionally categorized with peptide research compounds by vendors because its pharmacological target and clinical use (HPG axis modulation) overlap substantially with peptide therapeutics like gonadorelin and kisspeptin.

hCG is a potent agonist at the LH/hCG receptor (LHCGR), a Gs-coupled GPCR expressed on Leydig cells (males) and granulosa/luteal cells (females). It shares the same receptor with luteinizing hormone (LH) and exerts identical downstream signaling:

- **Males:** LHCGR activation on Leydig cells → cAMP/PKA → StAR protein induction → intratesticular testosterone (ITT) synthesis and secretion. Also stimulates Sertoli cell secretion of androgen-binding protein, supporting spermatogenesis. - **Females:** Midcycle LH/hCG surge → ovulation triggering, corpus luteum formation, and progesterone production.

The key pharmacological advantage over LH is half-life: hCG's additional O-linked glycosylation on the β-subunit extends plasma half-life to ~24–36 hours vs. ~60 minutes for LH. This allows 2–3x weekly dosing rather than continuous pulsatile delivery.

Unlike testosterone replacement therapy, hCG maintains the HPG axis signaling pathway and preserves intratesticular testosterone (which runs 50–100x higher than serum testosterone and is essential for spermatogenesis). TRT suppresses endogenous LH and FSH, causing testicular atrophy and azoospermia — effects that hCG prevents.