What is the Origin of d3-GHR Isoform?

The nomenclature originates from molecular genetics and endocrinology, specifically relating to the gene encoding the Growth Hormone Receptor (GHR) located on chromosome 5. The 'd3' signifies the deletion of exon 3 from the standard GHR transcript, a finding made possible by advanced genomic sequencing techniques. This discovery highlighted the complexity of gene splicing and its profound impact on hormonal signaling variability among the human population, contributing to personalized medicine.

What is the Mechanism of d3-GHR Isoform?

The absence of exon 3 alters the extracellular domain of the GHR, which is the precise site of GH binding and receptor dimerization. Functionally, the d3-GHR isoform generally exhibits enhanced signaling efficacy and increased sensitivity compared to the full-length GHR (fl-GHR) after binding to growth hormone. This increased receptor sensitivity leads to a stronger downstream signaling cascade, often resulting in higher circulating levels of insulin-like growth factor 1 (IGF-1) in response to both endogenous and administered GH.

d3-GHR Isoform ∞ Area

d3-GHR Isoform

Meaning

The d3-GHR isoform, also known as the growth hormone receptor (GHR) lacking exon 3, is a specific genetic variant of the human GHR found in a significant portion of the population. This splice variant is characterized by the absence of the third exon in the coding sequence, which results in a slightly shorter receptor protein structure. This structural difference influences the receptor’s binding affinity and subsequent signaling capability in response to growth hormone (GH). Its presence is clinically associated with variations in growth, body composition, and the individual metabolic response to therapeutic GH administration.