What is Semmorilin?

What is Sermorelin?

Sermorelin is a synthetic 29-amino acid peptide analogue of human growth hormone-releasing hormone (GHRH) that stimulates endogenous growth hormone (GH) secretion from the anterior pituitary gland. 1

Mechanism of Action

• Sermorelin has an amino acid composition identical to the N-terminal 29 amino acids of natural hypothalamic GHRH1-44, maintaining full biological activity of GHRH 1, 2
• It specifically stimulates GH secretion when administered intravenously or subcutaneously 1
• The peptide binds and activates the human GRF receptor, triggering endogenous GH release rather than providing exogenous hormone 2

Clinical Applications

Diagnostic Use

• Intravenous sermorelin 1 mcg/kg bodyweight serves as a rapid and relatively specific provocative test for diagnosing growth hormone deficiency 1
• It produces fewer false positive GH responses compared to other provocative tests in children without GH deficiency 1
• Normal GH responses to sermorelin cannot exclude GH deficiency due to hypothalamic deficits, requiring confirmation with subnormal responses to other provocative tests 1

Therapeutic Use in Children

• Once-daily subcutaneous sermorelin 30 mcg/kg bodyweight at bedtime is effective for treating prepubertal children with idiopathic growth hormone deficiency 1
• Significant increases in height velocity are sustained during 12 months of treatment, with limited data suggesting effects maintained for 36 months 1
• Sermorelin induces catch-up growth in the majority of GH-deficient children, with best responses in slow-growing, shorter children with delayed bone and height age 1

Emerging Applications

• In hypogonadal men on testosterone therapy, combination therapy with 100 mcg of sermorelin (plus GHRP-2 and GHRP-6) three times daily significantly increased serum IGF-1 levels from 159.5 ng/mL to 239.0 ng/mL (p<0.0001) after mean 134 days of treatment 3
• Preliminary research suggests sermorelin may have potential in recurrent glioma treatment by inhibiting tumor cell proliferation through cell cycle blocking and enhancing immune response 4

Pharmacokinetics

• The main limitation is its short plasma half-life of approximately 10-20 minutes in humans, caused by renal ultrafiltration and enzymatic degradation at the N-terminus 2
• Peak plasma levels are achieved 3 hours after subcutaneous injection 2
• PEGylation has been investigated to create more stable forms with longer half-life and increased pharmacodynamic response 2

Safety Profile

• Sermorelin is well tolerated with both single intravenous doses and repeated subcutaneous administration 1
• The most commonly reported adverse events are transient facial flushing and pain at injection site 1
• No serious adverse events have been consistently reported in clinical studies 1

Anti-Doping Considerations

• GHRH and its synthetic analogs, including sermorelin, are prohibited by the World Anti-Doping Agency (WADA) 5
• Detection methods using liquid chromatography-tandem mass spectrometry can identify sermorelin and its metabolites in urine at limits of detection of 1 ng/mL or less 5
• Nineteen major in vitro metabolites have been identified for detection purposes 5

Clinical Caveats

• The effect of long-term sermorelin treatment on final adult height remains undetermined 1
• Direct comparisons with somatropin show that sermorelin 30 mcg/kg/day produces smaller increases in height velocity than once-daily somatropin at the same dose 1
• Concurrent use of aromatase inhibitors or tamoxifen may result in smaller increases in IGF-1 levels when using sermorelin for GH augmentation 3