HGH (Somatropin)

Technical data

INN name

Human Growth Hormone (Somatropin)

CAS

12629-01-5

Molecular formula

C990H1528N262O300S7

Molecular weight

22124 g/mol

Identity and composition

Recombinant HGH (Somatropin, rhGH) is a polypeptide hormone of 191 amino acids and a molecular weight of 22,124 Da, with a sequence identical to endogenous pituitary human growth hormone (the 22 kDa isoform). It is produced by recombinant DNA technology in E. coli strains or in mammalian cells, folding with two intramolecular disulfide bridges (Cys53-Cys165 and Cys182-Cys189) that define its tertiary structure of four antiparallel alpha helices necessary for receptor recognition. Biological activity is expressed in International Units, with a reference equivalence of approximately 3 IU per milligram of pure protein. As the clinical reference form of hGH, somatropin is the comparative standard against which the analogs and secretagogues acting on the GH/IGF-1 axis are characterized, including AOD-9604, MOD-GRF (1-29), CJC-1295 and Ipamorelin. It is distributed lyophilized as a reagent for research (RUO) and requires reconstitution with bacteriostatic water before experimental handling.

Mechanism of action

Somatropin exerts its action by binding to the growth hormone receptor (GHR), a receptor of the class I cytokine superfamily present in liver, skeletal muscle, bone, kidney, and adipose tissue. A single hGH molecule induces the dimerization of two receptors, a reorientation that activates the associated JAK2 kinases and triggers the phosphorylation of the transcription factors STAT5b (the main pathway), in addition to the MAPK/ERK and PI3K/AKT cascades. The central consequence is the hepatic synthesis of IGF-1 (insulin-like growth factor 1), the mediator of most of the anabolic and mitogenic effects, which circulates forming a ternary complex with IGFBP-3 and the acid-labile subunit (ALS) that prolongs its half-life. In parallel, growth hormone produces direct effects independent of IGF-1: lipolysis and oxidation of fatty acids in the adipocyte, nitrogen retention and amino acid uptake in muscle, hepatic gluconeogenesis with a diabetogenic effect (insulin antagonism), renal retention of sodium and water, and stimulation of the growth plate in open epiphyses. Endogenous secretion is pulsatile and is regulated by the balance between stimulatory GHRH and inhibitory somatostatin, a pattern that exogenous administration of somatropin does not reproduce, unlike secretagogues that preserve physiological pulsatility.

Pharmacokinetics

After subcutaneous administration, somatropin is absorbed slowly from the depot, reaching maximum concentrations (Tmax) between 3 and 6 hours and with a bioavailability of close to 70-90% relative to the intravenous route. The terminal half-life is approximately 2 to 4 hours by the subcutaneous route, notably longer than the ~20 minutes observed after intravenous injection, because the rate of absorption from the subcutaneous tissue becomes the rate-limiting step. Clearance is predominantly renal (glomerular filtration and tubular degradation) and hepatic. The reference pharmacodynamic biomarker is not the concentration of the hormone itself but the IGF-1 response: IGF-1 and IGFBP-3 levels rise in a sustained manner for 24-48 hours after a dose, which allows the biological response to be monitored in research protocols through the IGF-1 generation test. The short half-life of the native hormone explains why the literature describes daily administration schedules, generally at nighttime to approximate the natural physiological peak of GH during slow-wave sleep.

Scientific evidence

Somatropin has decades of clinical evidence and is the therapeutic standard approved since 1985 for growth hormone deficiency, both pediatric and adult. There is consolidated evidence in indications such as Turner syndrome, Prader-Willi syndrome, chronic renal insufficiency with growth retardation, idiopathic short stature, and SHOX gene deficiency, as well as in HIV-associated lipodystrophy (approval of Serostim). The long-term safety profile is extensively documented in registries of tens of thousands of patients. It is important to note, within the strictly research-use-only (RUO) framework of this material, that recombinant growth hormone is not approved for anti-aging use or for athletic performance enhancement, contexts in which the evidence of benefit is scarce and the risk unfavorable; furthermore, it is included on the prohibited substances list of the World Anti-Doping Agency (WADA). The research literature uses it as a reference comparator against secretagogues and analogs that seek to stimulate the GH/IGF-1 axis in a more physiological way.

Research applications

In research contexts, somatropin is used as a reference tool for the study of the GH/IGF-1 somatotropic axis. Among its described experimental applications are: the IGF-1 generation test to characterize GH receptor sensitivity; the comparative study of the effect of secretagogues (CJC-1295, Ipamorelin, MOD-GRF, GHRP) versus the direct pattern of receptor stimulation; research on body composition and lipid metabolism owing to its direct lipolytic effect; models of JAK2/STAT5 signaling and of GH-induced insulin resistance; and studies of the pharmacokinetics and stability of recombinant therapeutic proteins. As a 191-amino-acid rhGH identical to the endogenous form, it serves as a positive control against which the responses of experimental molecules of the same axis are normalized.

Research protocols

The scientific literature describes the administration of somatropin by the subcutaneous route in daily doses, usually at night to synchronize with the physiological peak of GH secretion during sleep. Dosing is expressed in International Units (IU), with the reference equivalence of approximately 3 IU per milligram. In the reported schedules, rotation of injection sites (abdomen, thigh) is described to minimize local lipoatrophy, and monitoring of the response through serial measurement of IGF-1 and IGFBP-3, keeping them within the reference range for age and sex. Research protocols emphasize individualized adjustment and metabolic monitoring (blood glucose, thyroid function) because of the diabetogenic effect and the possible reduction of free T4. All handling corresponds strictly to research use (RUO).

Reconstitution

Lyophilized somatropin is reconstituted with bacteriostatic water (sterile water with 0.9% benzyl alcohol), added slowly down the wall of the vial to avoid the direct impact of the stream on the protein powder. The vial should be gently swirled in rotary motions; never shake it, since foam formation and shear stress denature and aggregate the 191-amino-acid protein, with loss of activity. The final concentration is calculated based on the volume of diluent added and the IU content of the vial, in order to dose reproducible volumes. A correctly reconstituted solution should be clear and colorless; any turbidity or visible particles indicate aggregation and loss of integrity. After reconstitution, the material is stored refrigerated and protected from light.

Stability and storage

In its lyophilized form and stored at 2-8°C, protected from light and moisture, somatropin maintains its stability for extended periods according to the batch specifications. Once reconstituted, the solution must be kept refrigerated at 2-8°C and used within a short window (typically up to 14-28 days depending on the preservative in the diluent), avoiding prolonged exposure to room temperature, direct light, and freeze-thaw cycles, which promote denaturation and the formation of high-molecular-weight aggregates. The protein is sensitive to heat, mechanical agitation, and pH extremes. The reconstituted solution must not be frozen. Visual verification of clarity before each use is the practical quality control of structural integrity in experimental handling.

Safety profile

Within the profile documented in the clinical literature, the adverse events associated with somatropin include: peripheral edema, arthralgia and myalgia, carpal tunnel syndrome and paresthesias (related to fluid retention), hyperglycemia and insulin resistance due to its antagonistic effect, suppression of the thyroid axis with a decrease in free T4, gynecomastia, and benign intracranial hypertension (pseudotumor cerebri). The described contraindications comprise active neoplasia (due to the mitogenic potential of IGF-1), proliferative diabetic retinopathy, acute critical illness, and sensitivity to the benzyl alcohol of the diluent. Reference monitoring consists of keeping IGF-1 within the therapeutic range without exceeding +2 standard deviations of the value expected for age and sex, together with monitoring of blood glucose and thyroid function. This material is a research-use-only (RUO) reagent; the safety information is provided for scientific purposes.

Comparative context

Compared with the growth hormone secretagogues, somatropin represents the direct replacement strategy: it supplies the exogenous 191-amino-acid hormone and saturates the GH receptor in a non-pulsatile manner, whereas GHRH analogs such as CJC-1295 and MOD-GRF (1-29), or GHRPs such as Ipamorelin and GHRP-6, stimulate endogenous release while preserving physiological pulsatility and the somatostatin feedback brake, which in the literature is associated with a distinct theoretical safety profile. Unlike AOD-9604 —a synthetic 176-191 fragment of hGH with lipolytic activity but without an effect on IGF-1 or on growth—, somatropin activates the complete GH→IGF-1 pathway. Compared with IGF-1 LR3, which acts directly on the IGF-1 receptor without passing through the GHR, somatropin operates one step higher in the cascade. This position as the reference native hormone is the reason it is used as the standard comparator in studies across the entire somatotropic axis.

History and development

Human growth hormone was isolated from the pituitary in 1956 and its 191-amino-acid sequence was determined in the following decades. Until the 1980s, the only source was extraction from cadaveric pituitary glands, a practice that was discontinued in 1985 when it was linked to cases of Creutzfeldt-Jakob disease from prions. That same year, recombinant DNA technology allowed the production of the first biosynthetic somatropin (Protropin, from Genentech, which included an additional methionine residue), followed by the exact 191-amino-acid sequence version (Humatrope). Recombinant production in E. coli and in mammalian cells eliminated the risk of prion transmission and ensured a scalable supply with a sequence identical to the endogenous hormone. The expiration of patents gave way to multiple rhGH biosimilars. This trajectory consolidated somatropin as the benchmark against which modern molecules of the GH/IGF-1 axis are developed and compared.

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Scientific references (7)

Peer-reviewed literature on HGH (Somatropin), with its PubMed identifier where available:

• Effects of Growth Hormone on Body Composition (Rudman D, et al. · New England Journal of Medicine · 1990) — Classic study on the effects of GH on body composition in older adults. PMID 2355952.
• Oxandrolone for growth hormone-treated girls aged up to 18 years with Turner syndrome. (Mohamed S, et al. · Cochrane Database Syst Rev · 2019) PMID 31684688.
• Efficacy, safety, quality of life, adherence and cost-effectiveness of long-acting growth hormone replacement therapy compared to daily growth hormone in children with growth hormone deficiency: A systematic review and meta-analysis. (Mameli C, et al. · Pharmacol Res · 2023) PMID 37236413.
• Multicentre clinical trial of authentic recombinant somatropin in growth hormone deficiency (Bierich · Acta Paediatrica Scandinavica Supplement · 1987) PMID 3324634.
• Antigenicity and efficacy of authentic sequence recombinant human growth hormone (somatropin): first-year experience in the United Kingdom (Buzi, et al. · Clinical Endocrinology · 1989) PMID 2691122.
• Recombinant DNA produced somatropin in the treatment of prepubertal growth hormone deficient children (Chang, et al. · Zhonghua Yi Xue Za Zhi (Chinese Medical Journal, Free China ed.) · 1991) PMID 1848467.
• Evaluation of the safety and efficacy of biosimilar recombinant growth hormone in children with growth hormone deficiency: non-inferiority, randomized, parallel, multicentric and Phase III trial (Zaeri, et al. · Expert Opinion on Drug Safety · 2025) PMID 38682328.

Otras presentaciones de HGH (Somatropina)

• HGH Frag 176-191

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