What is the Origin of d3-GHR Polymorphism?

The term is derived from "d3," indicating the deletion of exon 3, and "GHR," the abbreviation for Growth Hormone Receptor, combined with "polymorphism" to denote the common occurrence of this variant within the population. Its discovery arose from molecular genetic studies investigating the structural diversity of the GHR gene and its profound impact on growth hormone action in human physiology. The existence of two common GHR isoforms (fl-GHR and d3-GHR) underscores the complexity of the somatotropic axis regulation.

What is the Mechanism of d3-GHR Polymorphism?

The d3-GHR isoform, lacking the critical segment encoded by exon 3, is believed to exhibit altered dimerization properties or a slightly modified ligand binding affinity compared to the full-length receptor. This structural difference can lead to enhanced signaling efficiency upon binding of growth hormone, potentially resulting in a more potent biological response at the cellular level. The differential signaling capacity of the d3-GHR is thought to influence the downstream activation of the STAT5B pathway, ultimately modulating the hepatic synthesis of Insulin-like Growth Factor 1 (IGF-1) and other growth-related factors.

d3-GHR Polymorphism

Meaning

The d3-GHR polymorphism refers to a specific genetic variation in the human Growth Hormone Receptor (GHR) gene characterized by the deletion of the third exon (exon 3), resulting in a receptor isoform lacking 22 amino acids in the extracellular domain. This particular deletion, designated as d3-GHR, contrasts with the full-length (fl) GHR and represents a significant structural alteration of the receptor protein. Clinically, the presence of the d3-GHR allele is associated with differential sensitivity and response to exogenous growth hormone (GH) treatment, influencing growth, body composition, and metabolic outcomes. It is a key factor in personalized endocrinology, predicting therapeutic response.