The growth hormone receptor (GHR) relays growth hormone (GH) signals, a core example of receptor binding.
| Component |
Function |
| Extracellular domain |
GH binding |
| Transmembrane domain |
Membrane anchoring |
| Intracellular domain |
Signal transduction |
| JAK2 association |
Kinase activation |
One GH molecule binds two receptor chains that a 2018 review says are already paired.
| Step |
Event |
Significance |
| 1 |
GH binds first chain |
Initial contact |
| 2 |
GH binds second chain |
Pair repositioned |
| 3 |
JAK2 activation |
Signal initiation |
| 4 |
STAT5 phosphorylation |
Transcription |
| Component |
Role |
Outcome |
| JAK2 |
Receptor-associated kinase |
Signal amplification |
| STAT5b |
Transcription factor |
Gene expression |
| Target genes |
IGF-1, others |
Anabolic effects |
| Pathway |
Activation |
Effect |
| MAPK/ERK |
GH-dependent |
Cell proliferation |
| PI3K/Akt |
Cross-activation |
Survival, metabolism |
| SHP2 |
Signal modulation |
Regulatory |
| Tissue |
Primary Effect |
Mechanism |
| Liver |
IGF-1 production |
JAK-STAT |
| Muscle |
Protein synthesis |
Direct + IGF-1 |
| Fat |
Lipolysis |
Direct |
| Bone |
Growth |
IGF-1 mediated |
Mice lacking liver IGF-1 lost most blood IGF-1 yet grew normally (1999 study). See the IGF-1 signaling cascade and tissue-specific peptide effects.
| Factor |
Effect on Response |
| Age |
Decreases with age |
| Nutrition |
Fasting blunts GH action |
| Exercise |
May enhance |
| Chronic GH |
Possible downregulation |
| Strategy |
Claimed Purpose |
| Adequate protein |
Support IGF-1 output |
| Cycling GH peptides |
Maintain sensitivity (untested) |
| Exercise |
Receptor upregulation |
| Sleep |
Natural GH pulsatility |
In GH resistance, GH is present but IGF-1 stays low; fasting is the classic case (2014 review).
| Factor |
Effect |
| Fasting |
High GH, low IGF-1 |
| Inflammation |
Reduces GHR signaling |
| Obesity |
Lower GH secretion |
| Liver disease |
Reduced IGF-1 production |
Most of this is cell and mouse data. We found no human study testing whether secretagogues acting on the ghrelin receptor change GHR sensitivity.
