Orphan receptor GPR37L1 contributes to the sexual dimorphism of central cardiovascular control

Biol Sex Differ. 2018 Apr 6;9(1):14. doi: 10.1186/s13293-018-0173-y.


Background: Over 100 mammalian G protein-coupled receptors are yet to be matched with endogenous ligands; these so-called orphans are prospective drug targets for the treatment of disease. GPR37L1 is one such orphan, abundant in the brain and detectable as mRNA in the heart and kidney. GPR37L1 ablation was reported to cause hypertension and left ventricular hypertrophy, and thus, we sought to further define the role of GPR37L1 in blood pressure homeostasis.

Methods: We investigated the cardiovascular effects of GPR37L1 using wild-type (GPR37L1wt/wt) and null (GPR37L1KO/KO) mice established on a C57BL/6J background, both under baseline conditions and during AngII infusion. We profiled GPR37L1 tissue expression, examining the endogenous receptor by immunoblotting and a β-galactosidase reporter mouse by immunohistochemistry.

Results: GPR37L1 protein was abundant in the brain but not detectable in the heart and kidney. We measured blood pressure in GPR37L1wt/wt and GPR37L1KO/KO mice and found that deletion of GPR37L1 causes a female-specific increase in systolic, diastolic, and mean arterial pressures. When challenged with short-term AngII infusion, only male GPR37L1KO/KO mice developed exacerbated left ventricular hypertrophy and evidence of heart failure, while the female GPR37L1KO/KO mice were protected from cardiac fibrosis.

Conclusions: Despite its absence in the heart and kidney, GPR37L1 regulates baseline blood pressure in female mice and is crucial for cardiovascular compensatory responses in males. The expression of GPR37L1 in the brain, yet absence from peripheral cardiovascular tissues, suggests this orphan receptor is a hitherto unknown contributor to central cardiovascular control.

Keywords: Central nervous system; G protein-coupled receptors; Heart failure; Hypertension; Left ventricular hypertrophy; Mouse model of hypertension; Orphan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure*
  • Brain / metabolism
  • Female
  • Fibrosis
  • Kidney / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocardium / metabolism
  • Myocardium / pathology
  • Receptors, G-Protein-Coupled / physiology*
  • Sex Characteristics


  • Gpr37l1protein, mouse
  • Receptors, G-Protein-Coupled