The Exon 3-Deleted Growth Hormone Receptor (d3GHR) Polymorphism-A Favorable Backdoor Mechanism for the GHR Function

Area of Science:

• Endocrinology
• Genetics
• Pharmacology

Background:

• Growth hormone (GH) regulates growth and lifespan, with its receptor (GHR) being key to the GH/IGF-I axis.
• Two GHR isoforms, flGHR (full length) and d3GHR (lacking exon 3), have been identified.
• The d3GHR isoform is associated with increased receptor activity, improved signaling, and potential links to longevity.

Purpose of the Study:

• To review the complexity of GHR isoforms.
• To provide an overview of pharmacogenetic research on GHR isoforms.
• To highlight the ongoing and unresolved questions surrounding GHR and its isoforms.

Main Methods:

• Literature review of existing studies on GHR isoforms.
• Analysis of pharmacogenetic research findings.
• Examination of studies in various patient populations (acromegaly, Prader-Willi, Turner syndrome, SGA, GHD).

Main Results:

• The d3GHR isoform may affect receptor activity, signal transduction, and treatment response compared to the flGHR (WT) isoform.
• Studies suggest potential impacts of d3GHR on GH/IGF-I levels, height, weight, and BMI in specific conditions.
• Inconsistent results exist, potentially due to confounding factors like small sample sizes and varied methodologies.

Conclusions:

• The role and impact of GHR isoforms, particularly d3GHR, remain complex and require further investigation.
• Pharmacogenetic research on GHR isoforms is crucial for understanding individual responses to GH-related therapies.
• Clarifying the influence of GHR isoforms is essential for advancing knowledge in growth, development, and longevity.