Section 01
What it's used for
FDA-Approved for Child Growth Disorders
FDA-approved for children with growth hormone deficiency, Turner syndrome, Prader-Willi syndrome, being born small for gestational age, unexplained short stature, Noonan syndrome, and a shortage of the SHOX gene that affects bone growth.
▸Clinical wording
FDA-approved for GH deficiency, Turner syndrome, Prader-Willi syndrome, SGA, idiopathic short stature, Noonan syndrome, and SHOX deficiency.
FDA-Approved for Adult GH Deficiency
FDA-approved for adults with growth hormone deficiency. Research shows it improves body composition, such as more muscle and less fat, along with bone density, heart-disease risk markers, and quality of life in this group.
▸Clinical wording
FDA-approved for adult GHD showing improved body composition, bone density, cardiovascular risk profile, and quality of life.
Anti-Aging Use Is Controversial
Using growth hormone for age-related decline is controversial and not an approved use. In the TRIIM trial, healthy men treated with growth hormone plus DHEA and metformin showed thymus tissue regrowth and reversal of epigenetic age markers.
▸Clinical wording
Controversial use for age-related GH decline. TRIIM trial demonstrated thymic regeneration and epigenetic age reversal in healthy men treated with GH + DHEA + metformin.
FDA-Approved for HIV Wasting
FDA-approved under the brand name Serostim to treat wasting linked to HIV/AIDS — the severe, unwanted loss of body weight and muscle, also called cachexia, that can happen when the body breaks down tissue faster than it rebuilds it.
▸Clinical wording
FDA-approved (Serostim) for HIV-associated wasting and cachexia.
Section 02
Mechanism of Action
How the receptor flips on
- The receptor sits in the cell membrane already paired up before the hormone arrives.
- Hormone binding twists that pair so two attached enzymes can meet and switch each other on.
- Several laboratory techniques, including fluorescence measurement and protein structures, mapped this movement.
- A shutdown protein later marks the receptor for destruction; mice lacking it grow oversized with longer bones.
▸Clinical wording
GHR dimer reorientation and JAK2 trans-activation
The GH receptor is a 638-amino-acid homodimeric class I cytokine receptor that sits in the membrane as a preformed dimer before ligand arrives. FRET on the JAK2-binding motif, substitution of the extracellular domains with Jun zippers and docking of the JAK2 kinase and pseudokinase structures showed that GH binding switches the transmembrane helix pair from parallel to a left-handed crossover: the Box1 motifs separate, the inhibitory pseudokinase domain is lifted off the partner kinase domain, and the two kinase domains pair and trans-activate. SOCS2 later terminates the signal through ubiquitin-mediated degradation, and SOCS2-null mice are overgrown with longer long bones.
Carrying the message to the genes
- The switched-on enzyme tags the receptor so a messenger protein can dock and be activated.
- That messenger travels to the nucleus and turns on the gene for IGF-1, the growth factor.
- Children with a broken version of that messenger (STAT5B) fail to grow despite normal hormone.
- In mice, deleting liver IGF-1 collapsed blood levels without shortening the body or thigh bone.
▸Clinical wording
JAK2-STAT5 signalling and IGF1 gene transcription
Activated JAK2 phosphorylates tyrosines on the receptor intracellular domain; STAT5 docks there, is phosphorylated by JAK2, dimerises and moves to the nucleus to drive IGF1 transcription, while SHP-1 and SHP-2 dephosphorylate JAK2 and the STATs. STAT1 and STAT3 are also JAK2 substrates after GH, but STAT5 is the predominant transcription factor for GH-induced proliferative actions. Homozygous human STAT5B mutations give severe postnatal growth failure with normal or raised GH and low IGF-I, IGFBP-3 and ALS that do not rise on GH stimulation, usually with immune dysfunction. Liver-specific igf1 deletion in mice, by contrast, collapses circulating IGF-I without shortening body or femur length.
A second route inside the cell
- Growth hormone also switches on a different family of enzymes, bypassing the main one.
- That route raises calcium inside the cell and drives a separate growth-signalling cascade.
- A shape change in one receptor loop has been reported to steer this branch.
- All of this comes from cultured cell lines, not from measurements in whole animals.
▸Clinical wording
JAK2-independent SRC-family kinase and ERK signalling
Alongside the JAK2 route, GH activates SRC-family kinases, LYN in particular, independently of JAK2. LYN activates PLC-gamma, releasing inositol trisphosphate and diacylglycerol, raising intracellular calcium and activating RasGRP1, which feeds Ras and ERK1/2 phosphorylation; the receptor also engages the PI3K/Akt arm. An agonist-induced conformational change in the receptor F'G' loop has been reported to regulate this Src/ERK output separately from JAK2. These are cell-line observations rather than whole-organism measurements.
Burning fat and blunting insulin
- In human studies the clearest effect is a sharp rise in fat breakdown and blood fatty acids.
- Those rising fatty acids blunt insulin's action in the liver and the rest of the body.
- Effects on protein are modest at rest: slightly more building, slightly less breakdown and waste.
- During fasting the effects grow, and lacking the hormone raises protein loss by roughly half.
▸Clinical wording
Lipolysis and insulin antagonism as direct metabolic actions
In human studies the most prominent metabolic effect of GH is a marked rise in lipolysis and free fatty acid levels, with GH acting as a counterregulatory hormone that antagonises hepatic and peripheral insulin action through the accompanying FFA flux and uptake. Basal effects on protein metabolism are modest: increased whole-body and muscle protein synthesis, decreased breakdown, less amino-acid oxidation and less hepatic urea formation. During fasting the effects grow, and lack of GH raises protein loss and urea production by roughly 50%.
Changing how kidneys handle salt
- Rats exposed to very high hormone levels for a long time changed how they excreted sodium.
- Their kidney tubule cells showed higher pump activity and altered processing of a sodium channel.
- In a mouse kidney cell line the hormone raised production of that channel's main part.
- Blocking the growth hormone receptor stopped the transport change, tying it to the hormone.
▸Clinical wording
Renal sodium handling through STAT5 and alpha-ENaC
Rats chronically exposed to very high GH showed reduced furosemide-induced natriuresis and increased amiloride-stimulated natriuresis, with higher Na+/K+-ATPase activity and altered proteolytic maturation of epithelial sodium channel subunits in cortical collecting ducts. In a murine collecting-duct cell line, GH and IGF-I receptors signalled through JAK2/STAT5, ERK and AKT; GH induced alpha-ENaC mRNA, STAT5 was found bound to a response element in the alpha-ENaC promoter, and a GHR antagonist blocked the transport response.
Section 03
Biological Pathways
- GHR/JAK2/STAT5b IGF-1 axisGH reorients the GHR dimer, trans-activating JAK2, which phosphorylates STAT5b; STAT5b dimerizes, enters the nucleus, and drives IGF-1 gene transcription, later terminated by SOCS2.
- GHR/SRC/ERK proliferation armIndependent of JAK2, GH activates SRC-family kinase LYN, triggering PLC-gamma to raise calcium and activate RasGRP1, feeding Ras and ERK1/2 phosphorylation; a cell-line observation, not whole-organism data.
- GHR/PI3K/Akt glucose handlingGH engages PI3K/Akt for acute glucose uptake, but the accompanying rise in lipolysis and free fatty acids lets GH act as a counterregulatory hormone, producing chronic insulin resistance.
- Direct adipocyte lipolysisGH drives a direct rise in lipolysis and free fatty acids via HSL/ATGL activation in adipocytes; GH deficiency raises protein loss and urea production by roughly 50% during fasting.
Section 04
Dosage Information
191 amino acid single-chain polypeptide with two disulfide bonds| Route / system | Context | Range studied | Limitation |
|---|---|---|---|
| Subcutaneous — label, adult deficiency | FDA label, adult growth hormone deficiency | 0.2 mg a day to start (0.15–0.30), adjusted to IGF-I; by weight, up to 0.04 mg/kg a week, later 0.08. The start is 0.6 IU; 1 mg is 3 IU | The dose is set against IGF-I in people with a proven pituitary deficit. If growth hormone is already normal, there is nothing to replace and no target. |
| Subcutaneous — label, children | FDA label, growth hormone deficiency in children | 0.16–0.24 mg/kg a week in 6 or 7 injections — 0.48–0.72 IU/kg a week. On an 80 kg body that is 13–19 mg a week, about 5.5–8 IU a day | Per kilogram this is 4–6 times the adult dose, because the target is height at an open growth plate. Never tested in an adult — and quoted as if it were. |
| Subcutaneous — athlete trial | Randomised trial, 96 recreational athletes, 8 weeks | 2 mg a day — 6 IU, about 22–29 µg/kg at 70–90 kg — for 8 weeks | Sprint rose 3.9%; strength, power and endurance did not move, and the lean-mass gain was water outside the cells. Eight weeks says nothing about covert use. |
| Subcutaneous — 1990 ageing study | Healthy men aged 61–81, six months | 0.03 mg/kg three times a week — about 0.09 mg/kg a week, so 6.3–8.1 mg a week (19–24 IU) for a 70–90 kg man | Twelve men, picked for low IGF-I, no placebo. It measured body shape, not function; systolic pressure and fasting glucose rose. All anti-ageing use rests on it. |
| Subcutaneous — self-administration | Practice, for physique and anti-ageing | Doping reviews report 10–25 IU (3.3–8.3 mg) three or four times a week, mean nearer 4 IU a day; therapy is 1–2 IU a day. 1 mg is 3 IU | The unit is the error: a vial marked 12 IU holds 4 mg, and reading one for the other is a 3-fold mistake. Above 2 mg a day no healthy adult was ever trialled. |
Results
Syringe Fill Level (100u syringe)
Set positive values for: Recommended dose per kg.
Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.
Section 05
Protocols
No protocols featuring this peptide yet. Browse All Protocols
Section 06
Stability & Storage
Storing the product
Recombinant hGH is supplied as lyophilised powder or liquid formulations: liquid forms are kept at 2–8 °C, lyophilised ones at room temperature, depending on the product. Long-acting formulations such as somapacitan or lonapegsomatropin allow weekly dosing.
After opening
The protein is sensitive to shaking, heat, and freezing, and needs more careful handling than small peptides do. Exactly how long an opened pen or vial stays usable depends on the specific formulation and product instructions.
Section 07
Side Effects & Precautions
Reported effects of human growth hormone include common reactions, effects specific to children, and risks linked to long-term or excessive dosing.
Commonly reported effects
- Fluid retention (edema).
- Joint pain (arthralgia).
- Nerve compression in the wrist (carpal tunnel syndrome).
- Reduced insulin sensitivity and high blood sugar (insulin resistance, hyperglycemia).
- Headache.
Effects reported in children
- Slipped growth plate in the hip (slipped capital femoral epiphysis).
- Worsening of scoliosis (curved spine).
- Increased pressure inside the skull (intracranial hypertension).
Long-term cancer-risk concern
There is long-term concern about potential cancer risk, because IGF-1 is a growth factor. For approved indications, clinical data have not confirmed this risk.
Effects of excess dosing
Chronic dosing above normal physiological levels (supraphysiological dosing) can cause acromegalic features — physical changes associated with excess growth hormone.
Section 08
Regulatory Status
FDA / United States
Approved for specific conditions only
Approval covers growth hormone deficiency, several short-stature syndromes (Prader-Willi, Turner, Noonan, SHOX), small-for-gestational-age failure and chronic renal insufficiency — sold as Genotropin, Humatrope, Norditropin, Nutropin, Saizen, Serostim, Zomacton and Sogroya.
US criminal law
Off-label distribution is a federal felony
Under 21 U.S.C. §333(e), distributing or possessing hGH with intent to distribute for anything beyond an FDA-authorised, physician-prescribed use is a federal felony — up to 5 years, 10 if the recipient is a minor. Several states add their own controlled-substance rules on top.
WADA
Prohibited under S2.2.3, at all times
Growth hormone, its analogues (lonapegsomatropin, somapacitan, somatrogon) and fragments (AOD-9604, hGH 176-191) are a non-specified substance banned in and out of competition. No performance-based exemption exists — only a documented deficiency qualifies for a TUE.
EMA / Europe
Approved — and made biosimilar history
Omnitrope became the EMA's first-ever approved biosimilar in 2006, referencing Genotropin. The FDA also cleared it, but under a different legal pathway, since Omnitrope predates the US biosimilars law of 2010.
Regulatory status differs by country and changes over time. A prescription for one of the approved conditions above does not authorise any other use, and the criminal penalties described here are specific to US federal law.
Section 09
Research Studies
- [1]Mechanism of activation of protein kinase JAK2 by the growth hormone receptorBrooks AJ, Dai W, O'Mara ML, et al. · Science · 2014
- [2]A new mechanism for growth hormone receptor activation of JAK2, and implications for related cytokine receptorsWaters MJ, Brooks AJ, Chhabra Y. · JAK-STAT · 2014
- [3]The growth hormone receptor: mechanism of receptor activation, cell signaling, and physiological aspectsDehkhoda F, Lee CMM, Medina J, Brooks AJ. · Frontiers in Endocrinology · 2018
- [4]Growth hormone insensitivity associated with a STAT5b mutationKofoed EM, Hwa V, Little B, et al. · New England Journal of Medicine · 2003
- [5]Genetic defects in the growth hormone-IGF-I axis causing growth hormone insensitivity and impaired linear growthSavage MO, Hwa V, David A, Rosenfeld RG, Metherell LA. · Frontiers in Endocrinology · 2011
- [6]Normal growth and development in the absence of hepatic insulin-like growth factor IYakar S, Liu JL, Stannard B, et al. · Proceedings of the National Academy of Sciences · 1999
- [7]Gigantism in mice lacking suppressor of cytokine signalling-2Metcalf D, Greenhalgh CJ, Viney E, et al. · Nature · 2000
- [8]Effects of growth hormone on glucose, lipid, and protein metabolism in human subjectsMoller N, Jorgensen JO. · Endocrine Reviews · 2009
- [9]Epithelial sodium channel is a key mediator of growth hormone-induced sodium retention in acromegalyKamenicky P, Viengchareun S, Blanchard A, et al. · Endocrinology · 2008
Section 10
Frequently Asked Questions
In the one randomised trial of healthy exercising adults — 96 recreational athletes given 2 mg (about 6 IU) a day for 8 weeks — sprint performance rose by 3.9%, but strength, power and endurance did not change, and the reported increase in lean mass was mostly water retained outside muscle cells, not new tissue. The approved indications (pediatric and adult growth hormone deficiency, Turner and Prader-Willi syndromes, AIDS wasting) are all about restoring a documented deficit, not enhancing normal physiology. No controlled trial has shown HGH builds functional muscle or burns fat in a healthy adult with normal GH levels.
In human studies the most consistently measured metabolic effect of GH is a rise in fat breakdown and circulating free fatty acids, and this FFA flux directly antagonises insulin's action in liver and muscle. The 1990 ageing trial that anchors most anti-ageing use recorded a rise in fasting glucose alongside its body-composition changes. Insulin resistance and hyperglycemia are listed among the drug's recognised side effects, and chronic supraphysiological dosing can produce acromegaly-like features.
This remains an open question rather than a settled one. IGF-1, which GH stimulates the liver to produce, is a growth factor that promotes cell proliferation — the theoretical basis for concern — but clinical data from approved-indication use has so far been reassuring and has not shown a clear cancer signal. Long-term cancer incidence in healthy adults using GH outside those approved indications has not been directly measured.
In approved replacement therapy, dosing starts around 0.2 mg a day in adults and is adjusted against measured IGF-I levels, typically settling near 1–2 IU a day; the paediatric dose is 4–6 times higher per kilogram because it targets height at an open growth plate, not adult physiology. Doping-surveillance reviews describe self-administered use at roughly 10–25 IU, three or four times a week — several times the therapeutic range — a pattern never tested in a healthy adult trial. A common source of error is confusing IU and milligrams: one milligram equals three IU, and misreading the unit has caused serious overdoses.
HGH is FDA-approved by prescription only, under brand names including Genotropin, Humatrope, Norditropin and Serostim, and is classified as a controlled substance in some US states. WADA prohibits it under category S2, banned both in and out of competition. Outside a prescribed, monitored deficiency, its use for performance or physique purposes falls outside any approved indication.
It depends on the formulation: liquid HGH products are kept at 2–8 °C, while lyophilised (freeze-dried) powders can be stored at room temperature, depending on the specific product. The protein is sensitive to shaking, heat and freezing regardless of form, and how long an opened pen or vial stays usable varies by product, so manufacturer instructions govern rather than one universal rule.