Somatropin (191-aa Growth Hormone)

What Is Somatropin?

Somatropin is the generic name for recombinant human growth hormone, a highly purified protein produced by recombinant DNA technology that is equivalent to the growth hormone secreted by the human pituitary gland. It is used to replace endogenous growth hormone in children and adults with growth hormone deficiency.^[1][2]

Before recombinant production, growth hormone could only be obtained from cadaveric pituitary glands, a method first achieved by Maurice Raben at Yale in 1957. Recombinant growth hormone became available in 1985.^[3]

Somatropin is one of the most extensively studied protein drugs. Its evidence base includes randomized trials, systematic reviews and a real-world pediatric database of more than 83,000 treated children, as well as trials comparing it with newer long-acting growth hormone formulations.^[4][5]

Chemical Structure and Molecular Identity

Somatropin is a single-chain protein of 191 amino acids with the same sequence as native human growth hormone. PubChem has no compound record for it, so this page does not list a formula or molecular weight; as a large protein, it is characterized by biologic quality standards rather than small-molecule identifiers.

Somatropin preparations are produced by recombinant DNA technology, and at least one approved preparation is made in a mammalian cell line.^[1] Because it is a biologic, follow-on versions are regulated as biosimilars. Under European Medicines Agency guidelines, biosimilar somatropin products gained marketing authorization in the EU after demonstrating similarity to a reference product in quality, safety and efficacy.^[6]

Related long-acting forms

Several long-acting growth hormones have been engineered from or around the somatropin molecule to slow its removal from circulation. A 2023 review grouped them into four types: pegylated formulations, prodrugs converted into active drug, transient albumin-binding compounds and growth hormone fusion proteins. Somatrogon, a long-acting rhGH, is one example.^[3][5]

Research History and Development

Somatropin’s development history runs from pituitary extraction in the 1950s to recombinant production in 1985, followed by expanding indications, biosimilars and long-acting successors. Recombinant supply removed the dependence on cadaveric glands and widened access to therapy.^[3][2]

Over time, licensed pediatric uses grew beyond growth hormone deficiency. A 2010 systematic review prepared for a NICE technology appraisal listed licensed indications in children including growth hormone deficiency, Prader-Willi syndrome, Turner syndrome, chronic renal insufficiency and birth small for gestational age.^[7]

A gastrointestinal indication followed. A somatropin preparation produced in a mammalian cell line was described in 2005 as the only human growth hormone approved for short bowel syndrome in patients receiving specialized nutritional support.^[1] A 2022 review stated that phase 3 trials had verified the safety and efficacy of somatropin for improving intestinal adaptation.^[8]

More recent work has compared standard somatropin with long-acting rhGH. All four long-acting classes underwent phase 3 testing and showed noninferiority, with safety comparable to standard somatropin.^[3]

Mechanisms Studied in Research

Somatropin works by replacing or supplementing endogenous growth hormone, and research has examined its effects on linear growth, body composition, cardiovascular markers and intestinal adaptation. In children the therapeutic goals are linear growth and normal body composition.^[2]

Adult replacement

In adults with growth hormone deficiency, a 2013 review reported that rhGH restores normal body composition, improves cardiac function and normalizes cardiovascular risk factors such as low-density lipoprotein cholesterol and C-reactive protein.^[2]

Intestinal adaptation

After extensive bowel resection, growth hormone is one of several factors that regulate adaptation of the remaining intestine. A 2022 review described these effects as acting through stem cell proliferation and differentiation, apoptosis, angiogenesis and expression of nutrient-transport proteins.^[8] Somatropin is thought to enhance intestinal adaptation through direct or indirect effects on the intestine.^[9] Adaptation mainly occurs within about 2 years of surgery, and enteral feeding, glucagon-like peptide 2 and the gut microbiota also contribute; teduglutide, a long-acting GLP-2 analog, is the other approved agent in this setting.^[8]

Pharmacokinetic engineering

Long-acting growth hormones were designed to be absorbed rapidly but removed slowly from the circulation, with the aim of reducing treatment burden and improving adherence compared with standard somatropin.^[3]

Key Findings From Published Studies

Large clinical datasets show that somatropin increases short-term height gain and adult height across several pediatric conditions, while trials support its use in short bowel syndrome and as the comparator for long-acting growth hormones. Key findings by study type:

Real-world pediatric data

A 2022 analysis of an international database (1987-2012) covered 83,803 children treated with rhGH, most often for idiopathic growth hormone deficiency (46.9%). Median first-year height-SDS gain in prepubertal patients was 0.66 for idiopathic GH deficiency and 0.71 for small for gestational age. Median near-adult height-SDS gains reached 1.79 in boys and 2.07 in girls with idiopathic GH deficiency. Serious adverse events occurred in 3.7% of patients; the most common were craniopharyngioma recurrence, neoplasm, cancer and scoliosis. The authors concluded that rhGH increased short-term height gain and adult height across both GH-deficient and non-GH-deficient conditions.^[4]

Randomized trials

• Long-acting comparison: in a 12-month phase 3 trial in 228 prepubertal children with GH deficiency, height velocity was 10.10 cm/year with somatrogon and 9.78 cm/year with somatropin, meeting noninferiority. Mild to moderate adverse events occurred in 78.9% and 79.1%, respectively.^[5]
• Short bowel syndrome: in a randomized, double-blind study of 41 patients dependent on parenteral nutrition, somatropin alone or with glutamine produced significantly greater reductions in parenteral nutrition volume and calories than placebo plus glutamine. Adverse events were reported in all treated patients, though many also had symptoms before or after therapy.^[9] A separate review reported that combining growth hormone with an optimized diet and glutamine reduced long-term parenteral nutrition requirements in dependent patients.^[1]

Evidence gaps and safety

A systematic review found that of 30 randomized trials in children, only one reported final height, and it called for long-term trials covering outcomes such as quality of life.^[7] Reported adverse reactions include intracranial hypertension, fluid retention and glucose intolerance, with possible worsening of scoliosis and slipped capital femoral epiphysis in children. An increased risk of intracranial tumors has been reported in teenagers and young adults who had received head radiation for a first childhood neoplasm.^[2]

Because somatropin is a 191-amino-acid protein, its identity and purity are typically confirmed with HPLC and mass spectrometry data on a certificate of analysis.

Regulatory and Research Status

Somatropin is an approved prescription drug: it is indicated for growth hormone deficiency in children and adults and has been approved for short bowel syndrome. Approval applies to licensed pharmaceutical products made under regulatory oversight.^[2][1]

In the European Union, biosimilar somatropin products are authorized, while naming, interchangeability and substitution of biosimilars remain under discussion.^[6] Growth hormone is also prohibited in sport under the World Anti-Doping Agency’s Prohibited List.

A 2011 review noted that switching from an originator product to a biosimilar, or between biosimilars, requires specific consideration, and that pharmacovigilance and labeling of biosimilars were still being debated.^[6] Long-acting growth hormones based on pegylation, prodrug, albumin-binding and fusion-protein designs are available in some markets or approaching regulatory approval.^[3]