Somatropin

Human growth hormone (HGH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotropic cells of the anterior pituitary gland. Growth hormone plays an essential role in growth regulation during childhood as well as other basal metabolic functions, muscle and fat mass regulation, blood glucose level regulation, and lipid regulation in both children and adults. Synthesized in a strain of Escherichia coli, recombinant HGH is a polypeptide hormone that contains 191 amino acid residues with a molecular weight of 22 kDa. It has an identical primary protein structure to endogenous human growth hormone. Somatrem was the first available recombinant HGH and was largely replaced by somatropin, another form of recombinant HGH.

Growth hormone therapy is approved for various disorders of growth hormone deficiency, growth failure, or short stature including Turner syndrome, chronic renal insufficiency before transplantation, Prader-Willi syndrome, a history of fetal growth restriction, short stature homeobox (SHOX) haploinsufficiency, Noonan syndrome, idiopathic short stature, and adult- or childhood-onset growth hormone deficiency.

Somatotropin is a recombinant human growth hormone used as replacement therapy in various conditions of growth failure, growth hormone deficiency, and weakness in children and adults.

Somatotropin is indicated for the treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone, short stature associated with Turner syndrome, Prader-Willi syndrome (PWS), idiopathic short stature (ISS), short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, and short stature born small for gestational age (SGA). It is indicated for the treatment of growth failure in children associated with chronic kidney disease up to the time of renal transplantation.

It is also indicated for adults with adult-onset growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma. It is also used to treat childhood-onset growth hormone deficiency in adults due to congenital, genetic, acquired, or idiopathic causes.

Somatotropin is indicated for the treatment of wasting or cachexia in patients with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy to increase lean body mass and body weight and improve physical endurance.

Somatotropin is indicated for the treatment of short bowel syndrome in adult patients receiving specialized nutritional support.

• Adult Onset Growth Hormone Deficiency
• Cachexia
• Childhood-onset Growth Hormone Deficiency
• Growth Failure
• HIV Wasting Syndrome
• Short Bowel Syndrome (SBS)
• Short Stature

Somatotropin induces growth in nearly every tissue and organ in the body. It stimulates linear growth and cartilaginous growth of long bones. In children with short stature, growth hormone increases both the number and size of muscle cells. It also promotes the growth of internal organs, and it also increases red cell mass. By promoting nitrogen retention, growth hormone increases cellular protein synthesis. Growth hormone also retains potassium and phosphorus in the serum, which may be the result of cell growth. Growth hormone stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline. It has negligible effects on serum calcium levels. Although increased calcium excretion in the urine is observed, calcium absorption from the intestine is simultaneously enhanced. In end-stage renal disease, growth hormone was shown to improve several nutritional parameters, such as increases in serum insulin-like growth factor-I (IGF-I), serum albumin, and transferrin, as well as a reduction in blood urea nitrogen.

The metabolic effects of growth hormone are caused by the upregulation of insulin-like growth factor-1. Generally, growth hormone leads cells to enter an anabolic protein state with increased amino acid uptake, protein synthesis, and decreased catabolism of proteins. The diabetogenic effect of larger doses of growth hormone is well documented in the literature: somatotropin antagonizes insulin action in vivo, causing insulin resistance and glucose intolerance. It increases glucose production through gluconeogenesis and glycogenolysis from the liver and kidney and suppresses glucose uptake in the adipose tissue. In mice, growth hormone increased mRNA expression of 2 major gluconeogenic genes, phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase. The risk for impaired glucose tolerance and reduced insulin sensitivity may be increased in susceptible patients, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The development of new-onset type 2 Diabetes Mellitus was observed in patients receiving somatotropin treatment.

Growth hormone stimulates lipolysis via activation of the hormone-sensitive lipase in the adipose tissue, thereby increasing circulating levels of free fatty acids and triglycerides in the plasma. It also leads to a reduction of fat stores and decreased serum levels of low-density lipoprotein (LDL) cholesterol. In contrast to the effects seen in the adipose tissue, growth hormone promotes cellular uptake of free fatty acids in skeletal muscle by increasing the activity of lipoprotein lipase. Growth hormone may cause hyperinsulinism following beta-cell compensation for insulin resistance; however, there is some evidence that growth hormone directly promotes beta-cell proliferation and glucose-stimulated insulin secretion.

In conditions of growth failure, growth hormone deficiency, low body mass, and malnutrition, somatotropin treatment acts to mimic and restore the actions of endogenous growth hormone of stimulating linear bone growth, increasing bone mass, increasing muscle and reduced fat mass, and regulating blood glucose and lipid levels. Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage. Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.

At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.

When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m², the C_max ranged from 13.8 (±5.8) to 17.1 (±10.0) ng/mL and the T_max was four to five hours. Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean steady-state serum levels of approximately 23.1 (±15.0) ng/mL were reached at 150 minutes.

Information is unavailable.

While there is no information regarding the protein binding profile of recombinant human growth hormones, endogenous growth hormone is typically complexed with growth hormone-binding protein, which is a soluble form of growth hormone receptor, when it is incubated with plasma in vitro.

Information is unavailable.

When somatotropin was administered subcutaneously at the dose of 0.024 mg/kg or 3 IU/m², the mean apparent terminal half-life was Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the terminal elimination half-life was approximately 21.1 (±5.1) minutes.

Following intravenous infusion of 33 ng/kg/min of somatotropin in patients with growth hormone deficiency, the mean clearance rate was approximately 2.3 (±1.8) mL/min/kg or 139 (±105) mL/min.

The oral LD₅₀ is 242 mg/kg in rats and 828 mg/kg in mice. The inhalatory LD₅₀ is 710 mg/m³ and dermal LD₅₀ is 1100 mg/kg in rats. The intraperitoneal LD₅₀ in mice is 828 mg/kg.

Hypoglycemia followed by hyperglycemia, possibly with fluid retention, can be observed in somatropin overdose. Long-term or excessive use of growth hormone can lead to the signs and symptoms of gigantism and acromegaly.

No interactions found.

• Pediatric growth hormone deficiency: 0.024 to 0.034 mg/kg/day, 6 to 7 times a week.
• Noonan Syndrome: Up to 0.066 mg/kg/day.
• Turner Syndrome: Up to 0.067 mg/kg/day.
• Short stature born small for gestational age (SGA): Up to 0.067 mg/kg/day.
• Adult growth hormone deficiency: 0.004 mg/kg/day to be increased as tolerated to not more than 0.016 mg/kg/day after approximately 6 weeks, or a starting dose of approximately 0.2 mg/day (range, 0.15 to 0.30 mg/day) increased gradually every 1 to 2 months by increments of approximately 0.1 to 0.2 mg/day.