Growth response to growth hormone‐releasing hormone(1–29)‐NH₂ compared with growth hormone

Abstract

To assess the growth‐promoting effect of different doses of growth hormone‐releasing hormone(1–29)‐NH, (GHRH(1–29)‐NH2) in GH deficiency (GHD) of hypothalamic origin, 43 prepubertal children aged between 4.3 and 18.9 years (mean 10.4 k 2.9 years) were randomly assigned to three treatment regimens: low‐dose GHRH(1–29)‐NH2 (LD group; n = 15), high‐dose GHRH(1–29)‐NH, (HD group; n = 12) and GH (GH group; n = 16). The LD group received GHRH(1–29)‐NH, at 30 yglkglday S.C. in three daily doses, the HD group received 60 μg/kg/day S.C. in three daily doses and the GH group received GH, 0.1 IU/kg/day S.C. once daily. All children were treated for a period of 6 months. Evaluation included anthropometry, bone age, intravenous and subcutaneous GHRH(1–29)‐NHZ tests and determination of insulin‐like growth factor I (IGF‐I) levels. An increase in height velocity of 2 cm/year or more was observed in all except two children. Height velocity during treatment was lowest in the LD group, but comparable in the HD and GH groups. An increase in height SDS for bone age occurred only in the GH‐treated group. GH responses to intravenous GHRH(1–29)‐NH, showed a priming effect of the LD GHRH(1–29)‐NH, treatment, while a decrease in response occurred in the GH‐treated group. Following a subcutaneous test dose of one‐third of the daily dose of GHRH(1–29)‐NH, GH levels remained unchanged in both the LD and HD groups. There was accumulation of GHRH immunoreactivity over time in the HD group, but there was no correlation between measured GHRH and GH levels. IGF‐I levels increased in the HD and GH‐treated groups. Antibodies to GHRH were detected in 54% and 58% of children in the LD and HD groups, respectively. None of these variables correlated with changes in height velocity. The results indicate that 6 months of GH and high‐dose GHRH(1–29)‐NH, treatment have similar growth‐promoting effects.

An immuno polymerase chain reaction screen for the detection of CJC‐1295 and other growth‐hormone‐releasing hormone analogs in equine plasma

“…These results highlight not only the challenge of policing the use of these non‐conjugated drugs through blood testing, but also the poor stability of most peptide‐based drugs that limits their pharmacological effects. Despite the short detection window, the effective use of mGRF 1–29 requires regular high doses of the peptide, making detection of the drug more likely …”

“…Despite the short detection window, the effective use of mGRF 1-29 requires regular high doses of the peptide, making detection of the drug more likely. 26 With the advent of strategies such as micro-dosing that are designed to thwart screening tests, there is a need to develop ever more sensitive drug detection assays. The sensitivity and specificity Detection of mGRF 1-29 in equine plasma following drug administrationthe concentration profile of mGRF 1-29 in equine plasma was monitored over 6 hours using the I-PCR assay after the third of three daily administrations of 500 μg of mGRF 1-29 by intramuscular injection.…”

Growth hormone secretagogues: history, mechanism of action, and clinical development

“…58 Sermorelin rapidly and specifically increased GH release in healthy children but not in those with GH deficiency compared with existing provocative tests, 59 resulting in an approval for this indication by the FDA in 1990. Subsequently, 6 months treatment with sermorelin showed a significant increase in GH release and growth velocity in GHdeficient children, 60,61 and preliminary data suggested the efficacy of sermorelin treatment for 36 months. 59 Based on these findings, sermorelin was approved by the FDA for the Growth hormone secretagogues: history, mechanism of action and clinical development treatment of idiopathic GH deficiency in children with growth failure in 1997.…”

State-of-the-Art Clinical Results of Growth Hormone Secretagogues, SARM and Antagonists

“…Sermorelin increased GH release rapidly and specifically in healthy children, but not in those with GH deficiency, compared to existing provocative tests, resulting in approval for this indication by the FDA in 1990 [24]. Subsequently, the 6-month treatment with sermorelin showed a significant increase in GH release and growth speed in children with GH deficiency [25,26], and preliminary data suggested the efficacy of treatment with sermorelin for 36 months [24]. Based on these findings, sermorelin was approved by the FDA for the treatment of idiopathic GH deficiency in children with failed growth in 1997.…”