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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PRLH
prolactin releasing hormone
Chromosome 2 · 2q37.3
NCBI Gene: 51052Ensembl: ENSG00000071677.2HGNC: HGNC:17945UniProt: P81277
14PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
response to peptide hormoneneuropeptide hormone activityprolactin-releasing peptide receptor bindingG protein-coupled receptor signaling pathwayBenign Thyroid Gland Neoplasmprostate carcinomaprostate cancerobesity due to melanocortin 4 receptor deficiency
✦AI Summary

PRLH (prolactin-releasing hormone) is a neuropeptide that functions primarily in energy homeostasis rather than prolactin regulation. The peptide signals through the G protein-coupled receptor GPR10 to regulate feeding behavior and body weight 1. PRLH-expressing neurons in the nucleus tractus solitarius (NTS) represent a critical neural circuit component for long-term energy balance control. Activation of NTS Prlh neurons suppresses food intake, overcomes orexigenic hypothalamic signals (such as those from AgRP neurons), and ameliorates obesity in both high-fat diet-challenged and genetically obese mice 2. This appetite-suppressive function operates independently of prolactin secretion pathways 3. Recent evidence demonstrates that NTS Calcr/Prlh neurons show sustained transcriptional changes in response to anti-obesity amylin analogs in rodent models, with increased Prlh expression correlating with long-term weight loss 4. PRLH also participates in nicotine-mediated feeding regulation 5. While initially identified as a prolactin-releasing factor, PRLH's physiological role centers on appetite suppression and metabolic homeostasis, making it a potential therapeutic target for obesity treatment.

Sources cited
1
PRLH (prolactin-releasing peptide) acts as a ligand for GPR10 receptor
PMID: 18204826
2
NTS Prlh neurons suppress food intake, overcome AgRP-driven hyperphagia, and ameliorate obesity
PMID: 34462445
3
PRLH functions as a prolactin-releasing peptide with broader neuroendocrine roles beyond direct lactotroph stimulation
PMID: 12763633
4
NTS Calcr/Prlh neurons show sustained increased Prlh expression with long-term cagrilintide treatment in rats, correlating with weight loss
PMID: 39868309
5
PRLH is an energy homeostasis-related neuron involved in feeding regulation
PMID: 39826824
Disease Associationsⓘ20
Benign Thyroid Gland NeoplasmOpen Targets
0.28Weak
prostate carcinomaOpen Targets
0.12Weak
prostate cancerOpen Targets
0.09Suggestive
obesity due to melanocortin 4 receptor deficiencyOpen Targets
0.08Suggestive
obesity due to pro-opiomelanocortin deficiencyOpen Targets
0.06Suggestive
breast neoplasmOpen Targets
0.06Suggestive
obesity due to leptin receptor gene deficiencyOpen Targets
0.06Suggestive
obesity due to prohormone convertase I deficiencyOpen Targets
0.06Suggestive
hypoinsulinemic hypoglycemia and body hemihypertrophyOpen Targets
0.06Suggestive
breast cancerOpen Targets
0.06Suggestive
lipodystrophy, congenital generalized, type 5Open Targets
0.05Suggestive
obesity and hypopigmentationOpen Targets
0.05Suggestive
MODYOpen Targets
0.05Suggestive
obesity due to congenital leptin deficiencyOpen Targets
0.05Suggestive
obesity due to SIM1 deficiencyOpen Targets
0.05Suggestive
LIPE-related familial partial lipodystrophyOpen Targets
0.05Suggestive
PLIN1-related familial partial lipodystrophyOpen Targets
0.05Suggestive
severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiencyOpen Targets
0.05Suggestive
CIDEC-related familial partial lipodystrophyOpen Targets
0.05Suggestive
hyperinsulinism due to HNF1A deficiencyOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NPFFProtein interaction94%NPFFR2Protein interaction79%QRFPProtein interaction78%PRLProtein interaction75%NPVFProtein interaction74%PRLHRProtein interaction72%
Tissue Expression6 tissues
Brain
0%
Ovary
0%
Heart
0%
Liver
0%
Bone Marrow
0%
Lung
0%
Gene Interaction Network
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PRLHNPFFNPFFR2QRFPPRLNPVFPRLHR
PROTEIN STRUCTURE
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PDB9K27 · 2.68 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.95LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.81 [0.90–1.95]
RankingsWhere PRLH stands among ~20K protein-coding genes
  • #15,968of 20,598
    Most Researched14
  • #17,702of 17,882
    Most Constrained (LOEUF)1.95
Genes detectedPRLH
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
A Cross-Species Atlas of the Dorsal Vagal Complex Reveals Neural Mediators of Cagrilintide's Effects on Energy Balance.
PMID: 39868309
bioRxiv · 2025
1.00
2
Prolactin-releasing peptide.
PMID: 18204826
Results Probl Cell Differ · 2008
0.90
3
NTS Prlh overcomes orexigenic stimuli and ameliorates dietary and genetic forms of obesity.
PMID: 34462445
Nat Commun · 2021
0.80
4
Prolactin-releasing peptides.
PMID: 12763633
Regul Pept · 2003
0.70
5
[Prolactin-releasing peptide (PrRP)].
PMID: 16149497
Nihon Rinsho · 2005
0.60