Overview
Human Growth Hormone (HGH), also known as somatropin or somatotropin, is a 191-amino acid, single-chain polypeptide hormone produced by somatotropic cells in the anterior pituitary gland. It is one of the most important hormones in the human body, playing critical roles in growth, metabolism, cell regeneration, and body composition.
Recombinant human growth hormone (rhGH) has been available since 1985 and is bioidentical to endogenous HGH. It represents a cornerstone in endocrinology research and serves as the foundation for understanding all growth hormone-related peptides, including secretagogues like GHRP-6, Ipamorelin, and Sermorelin.
Molecular Structure
HGH has a distinctive four-helix bundle structure stabilized by two intramolecular disulfide bonds:
- Cys53-Cys165: Forms a large loop in the molecule
- Cys182-Cys189: Forms a small loop near the C-terminus
The mature protein is derived from a 217-amino acid precursor through cleavage of a 26-amino acid signal peptide. The molecular weight is approximately 22,124 Da with an isoelectric point of 5.2.
Mechanism of Action
GH-IGF-1 Axis
HGH exerts its effects through both direct and indirect mechanisms:
Direct Effects:
- Binds to the transmembrane Growth Hormone Receptor (GHR)
- Activates intracellular JAK2 (Janus kinase 2)
- Triggers STAT5 (Signal Transducer and Activator of Transcription 5) signaling
- Promotes lipolysis and glucose regulation
Indirect Effects (via IGF-1):
- Stimulates hepatic production of Insulin-like Growth Factor 1 (IGF-1)
- IGF-1 activates the PI3K/Akt and MAPK/ERK pathways
- Promotes protein synthesis, cell proliferation, and anti-apoptotic effects
- Mediates the majority of HGH's growth-promoting effects
Downstream Signaling Pathways
- JAK2-STAT5 Pathway: Primary signaling cascade for GH effects
- PI3K/Akt Pathway: Cell survival and metabolic regulation
- MAPK/ERK Pathway: Cell proliferation and differentiation
FDA-Approved Indications
Pediatric Uses
- Growth Hormone Deficiency (GHD): Both idiopathic and organic causes
- Turner Syndrome: Chromosomal disorder affecting females
- Prader-Willi Syndrome: Genetic disorder with growth failure
- Chronic Renal Insufficiency: Growth failure before kidney transplant
- Idiopathic Short Stature (ISS): Children with unexplained short stature
- Small for Gestational Age (SGA): Children who fail to catch up by age 2-4
- SHOX Deficiency: Short stature homeobox-containing gene deficiency
- Noonan Syndrome: Genetic disorder affecting growth
Adult Uses
- Adult Growth Hormone Deficiency: Childhood-onset or adult-onset GHD
- HIV-Associated Wasting: Treatment of AIDS wasting syndrome (Serostim)
- Short Bowel Syndrome: In patients receiving specialized nutritional support
Pharmacokinetics
| Parameter | Value |
|---|---|
| Route of Administration | Subcutaneous injection (preferred), IM, IV |
| Bioavailability | ~70-90% (SC) |
| Half-life (IV) | 18-20 minutes |
| Half-life (SC) | 2-4 hours (absorption-limited) |
| Time to Peak | 3-6 hours (SC) |
| Metabolism | Liver and kidney |
| Dosing Frequency | Once daily (typically evening) |
Clinical Research Summary
Long-term Safety Data
A comprehensive study of 15,809 GH-treated patients (mean follow-up 5.3 years) demonstrated:
- Adverse events reported in 51.2% of patients (treatment-related in 18.8%)
- De novo cancer incidence comparable to general population (SIR 0.92)
- Most common side effects: fluid retention, joint pain, injection site reactions
Efficacy in GHD
- Significant improvements in body composition (decreased fat mass, increased lean mass)
- Enhanced bone mineral density
- Improved lipid profiles
- Better quality of life scores
Safety Profile
Common Side Effects
- Peripheral edema and fluid retention
- Arthralgia (joint pain)
- Myalgia (muscle pain)
- Paresthesia (numbness/tingling)
- Injection site reactions
- Carpal tunnel syndrome
Serious Warnings
- Critical Illness: Contraindicated in acute critical illness (increased mortality risk)
- Cancer History: May increase risk of tumor recurrence in childhood cancer survivors
- Diabetes: May unmask latent diabetes or worsen glucose control
- Intracranial Hypertension: Rare cases of increased intracranial pressure
Contraindications
- Active malignancy
- Acute critical illness
- Active proliferative diabetic retinopathy
- Closed epiphyses (for growth promotion)
- Prader-Willi syndrome with severe obesity or respiratory impairment
Comparison with GH Secretagogues
Unlike Growth Hormone Releasing Peptides (GHRPs) and Growth Hormone Releasing Hormone (GHRH) analogs, HGH is the actual hormone rather than a stimulator of its release:
| Compound | Mechanism | Pulsatile Release | Feedback Preserved |
|---|---|---|---|
| HGH | Direct hormone replacement | No | No |
| GHRH Analogs (Sermorelin, CJC-1295) | Stimulate GH release | Yes | Yes |
| GHRPs (GHRP-6, Ipamorelin) | Ghrelin mimetic | Yes | Partially |
Available Formulations
Brand Names:
- Genotropin (Pfizer)
- Humatrope (Eli Lilly)
- Norditropin (Novo Nordisk)
- Nutropin AQ (Genentech)
- Omnitrope (Sandoz)
- Saizen (EMD Serono)
- Zomacton (Ferring)
- Serostim (EMD Serono) - HIV wasting
Long-Acting Formulations:
- Skytrofa (lonapegsomatropin) - Once-weekly administration
Research Directions
Current research focuses on:
- Long-acting GH formulations reducing injection frequency
- Combination therapies for specific conditions
- Role in aging and metabolic disorders
- Optimal dosing strategies for different populations
Important Disclaimers
HGH is a prescription medication with strict regulations. The FDA has not authorized HGH use for:
- Anti-aging purposes
- Athletic performance enhancement
- Bodybuilding
Distribution of HGH for unapproved uses is a federal offense. All research and clinical use should follow established medical guidelines and regulatory requirements.
References
Key sources include peer-reviewed literature from the Journal of Clinical Endocrinology & Metabolism, FDA prescribing information, and established clinical guidelines from the Endocrine Society.