Prolactin sparing secretagogues are a specialized class of Growth Hormone Secretagogues (GHS) that are designed to stimulate the release of endogenous Growth Hormone (GH) while exhibiting minimal or negligible effect on the co-secretion of the hormone prolactin. Prolactin elevation is an undesirable side effect of some older GHS compounds, as high levels can lead to sexual dysfunction and pituitary dysregulation. The ‘sparing’ feature is a key pharmacological refinement, ensuring the therapeutic benefits of GH enhancement are achieved without compromising the integrity of the endocrine axes.
Origin
This terminology emerged from the clinical refinement of Growth Hormone Secretagogue research. Initial GHRP compounds were found to also activate prolactin release, leading to unwanted side effects. Subsequent drug design focused on creating molecules, such as Ipamorelin, that maintain high selectivity for the GHS receptor (GHS-R1a) while avoiding cross-reactivity with prolactin-releasing pathways. This represents a significant advancement in peptide safety and specificity.
Mechanism
The mechanism of these secretagogues involves highly selective agonism at the GHS-R1a receptor, coupled with a precise structure that avoids the activation of the lactotroph cells responsible for prolactin secretion. Unlike less selective agents, these compounds do not significantly interfere with the dopaminergic inhibition of prolactin release. This targeted action ensures a clean, pulsatile surge of GH while maintaining the critical dopaminergic and somatostatinergic control over prolactin and other pituitary hormones.
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