Growth Hormone (Somatropin)

Mechanism of Action

Recombinant human growth hormone (rhGH/somatropin) is a 191-amino acid protein identical to endogenous GH. It binds the GH receptor (GHR), a type I cytokine receptor, activating the JAK2-STAT5 signaling cascade that drives hepatic IGF-1 production — the primary mediator of GH's anabolic effects. GH directly stimulates lipolysis via hormone-sensitive lipase (HSL) activation and inhibits lipogenesis. It promotes chondrocyte proliferation, collagen synthesis, and linear bone growth. GH also enhances protein synthesis through mTOR pathway activation and improves nitrogen balance. Pulsatile secretion patterns are important — continuous GH exposure preferentially drives IGF-1, while pulsatile release favors direct lipolytic effects.

Dosing Protocol

Notes

GH is among the most powerful body composition agents available but carries significant risks with improper use. CRITICAL: Always check IGF-1 levels — do not dose by 'feel.' Supraphysiological IGF-1 (>300 ng/mL) is associated with increased cancer risk in epidemiological data. GH increases T4-to-T3 conversion — check thyroid function within 6-8 weeks of initiation. GH also increases cortisol clearance — may unmask adrenal insufficiency. Required bloodwork: IGF-1 (target upper-normal for age), fasting glucose, fasting insulin, HbA1c, free T4, free T3, TSH, cortisol (AM), CBC, CMP, lipid panel. Monitor every 3 months during titration, every 6 months once stable. DEXA scan annually for body composition tracking. Colonoscopy screening at appropriate intervals (IGF-1 and colon polyp risk). Medical supervision required.

Stacking

• Testosterone (synergistic body composition effects)
• MK-677 / GH secretagogues (some use on GH-off days)
• T3/T4 thyroid hormones (GH increases T4-to-T3 conversion)
• Insulin (advanced — manages GH-induced insulin resistance)

Interactions

• Insulin [HIGH] — GH induces insulin resistance by opposing insulin signaling at the post-receptor level. Monitor fasting glucose and HbA1c closely.
• Glucocorticoids (Cortisol) [MEDIUM] — Supraphysiological cortisol inhibits GH secretion and IGF-1 production. GH may also reduce 11beta-HSD1 activity, unmasking relative hypocortisolism.
• Thyroid hormones [MEDIUM] — GH increases peripheral T4-to-T3 conversion; may unmask subclinical hypothyroidism or require thyroid dose adjustment.
• Oral estrogens [MEDIUM] — Oral estrogen reduces hepatic IGF-1 production via first-pass effect, blunting GH efficacy.

Contraindications

• Active malignancy (GH/IGF-1 promotes cell proliferation)
• Active proliferative or preproliferative diabetic retinopathy
• Acute critical illness (GH increased mortality in ICU patients)
• Active intracranial lesion or tumor
• Prader-Willi syndrome with severe obesity or respiratory impairment
• Closed epiphyses (for linear growth indication only)

Side Effects

• Fluid retention and edema (dose-dependent, typically resolves in 2-4 weeks)
• Carpal tunnel syndrome and joint pain
• Insulin resistance and elevated fasting glucose
• Headache
• Numbness and paresthesias
• Potential increased cancer risk with chronic supraphysiological IGF-1 levels
• Gynecomastia
• Acromegalic features with long-term excessive dosing (jaw growth, digit enlargement)

Key Papers

• 10.1210/jc.2005-1726
• 10.1210/jc.2006-0546
• 10.1056/NEJMoa072557

Source Quality

FDA-approved pharmaceutical products (Genotropin, Norditropin, Humatrope, Omnitrope, Saizen). Only use pharmaceutical-grade rhGH — 'generic GH' from non-pharmaceutical sources often contains bacterial endotoxins, incorrect amino acid sequences, or degradation products. Cold chain integrity is critical (2-8C storage).

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