HGH (somatropin, research reference) dosage protocol

What the compound is

Human growth hormone (hGH), also known as somatropin, is a protein hormone. Historically, hGH was extracted from human pituitaries, with the first human receiving GH therapy in 1956 (PMID 22081428). Availability was limited, requiring many human pituitaries for treatment, until synthetic recombinant hGH (rhGH) became available (PMID 22081428).

hGH can exist in different forms, including a 20 kDa isoform (20K hGH-V) derived from the GH2 gene, which has different properties compared to hGH derived from the GH1 gene (PMID 40524488). Fragments of hGH, such as AOD9604 (a C-terminal fragment), can also act in ways novel to traditional hGH-stimulated pathways (PMID 11673763). Pegvisomant is a pegylated, genetically modified hGH developed to prevent GH receptor activation, used in treatments for acromegaly (PMID 15134290).

How it is thought to work

hGH exerts its effects by activating receptors. However, hGH fragments like AOD9604 do not compete for the hGH receptor and do not induce cell proliferation, unlike hGH (PMID 11673763). This suggests that hGH may behave as a pro-hormone, with fragments acting via different mechanisms (PMID 11673763). Pegvisomant, in contrast, works by preventing GH receptor activation (PMID 15134290).

The 20K hGH-V isoform has been shown to promote growth but lacks the diabetogenic and lactogenic activities of hGH. In cells, placental growth hormone (hGH-V) gene expression and promoter activity are influenced by glucose concentration and demethylating conditions (PMID 20005926). Site-specific PEGylation of hGH, which involves attaching poly(ethylene glycol), can increase the systemic exposure and half-life of hGH conjugates by 4.5-fold in animals, while preserving its native-like secondary structures (PMID 23432141).

What laboratory and animal studies report

In obese mice, chronic treatment with hGH or AOD9604 significantly reduced body weight gain, increased fat oxidation, and stimulated lipolysis (PMID 11673763). Unlike hGH, AOD9604 did not induce hyperglycemia or reduce insulin secretion in these mice (PMID 11673763).

Studies in GH knockout mice compared hGH and 20K hGH-V. 20K hGH-V-treated mice had similar body size and composition to hGH-treated mice, but improved insulin sensitivity despite similar adipose tissue mass (PMID 40524488). 20K hGH-V treatment altered adipose and muscle gene expression differently than hGH. In adipose tissue, 20K hGH-V decreased genes associated with T and B lymphocytes and increased genes for adipogenesis and carbon metabolism compared to hGH (PMID 40524488). In muscle tissue, 20K hGH-V upregulated pathways for electron transport chain and muscle contraction (PMID 40524488).

In prolactin receptor-positive cancer cells, 20K hGH-V exhibited significantly less growth compared to hGH treatment (PMID 40524488). In human placental choriocarcinoma cells, high glucose diminished hGH-V mRNA levels, while 5-azacytidine increased hGH-V gene expression (PMID 20005926).

Human evidence so far

The first human to receive GH therapy was in 1956 for metabolic balance studies (PMID 22081428). By 1959, native hGH collected from human pituitaries was given to presumed GH deficient patients (PMID 22081428). Cases of Creutzfeldt-Jakob disease (CJD) linked to contaminated hGH produced years earlier led to the discontinuation of its distribution and use in 1985, around the time synthetic rhGH became available (PMID 22081428). Pegvisomant is available in the US and Europe for the treatment of acromegaly (PMID 15134290).

Key terms explained

Adipogenesis: The process of fat cell formation (PMID 40524488).

Diabetogenic: Causing or tending to cause diabetes (PMID 40524488).

hGH-V: A variant of human growth hormone, such as the 20 kDa isoform (20K hGH-V) or placental growth hormone (PMID 40524488, PMID 20005926).

Lactogenic: Stimulating milk production (PMID 40524488).

Lipolysis: The breakdown of fats and other lipids by hydrolysis to release fatty acids (PMID 11673763).

Pegylated: A process where poly(ethylene glycol) (PEG) molecules are attached to another molecule, often to improve drug properties like half-life (PMID 23432141).

Transcriptomics: The study of the complete set of RNA transcripts produced by an organism or a specific cell or tissue type (PMID 40524488).