Disease relevance of Ghrhr

• To study the influence of GHRH in autoimmunity, susceptibility to experimental autoimmune encephalomyelitis (EAE) was examined in C57BL/6J-Ghrhr(lit/lit) (lit/lit), mice deficient in the GHRHR gene [1].
• These disorders are controlled by defective alleles at major loci referring to hormones or hormone receptors, e.g. growth hormone receptor for the recessive sex-linked dwarfism (dw) in chickens and the recessive autosomal Laron-type dwarfism in man, and growth hormone releasing hormone receptor for the recessive "little" mutation (lit) in mice [2].
• Evaluation of 21 specimens of human primary endometrial carcinoma for expression of SV1 by immunohistochemistry indicated that in contrast to the GHRH receptor, which is absent, SV1 is expressed in approximately 43% of the specimens [3].
• The mRNA expression for GHRH receptor splice variants was found in all these models of prostate cancer [4].

High impact information on Ghrhr

• We report that the Ghrhr gene is located in the middle of mouse chromosome 6 in the same region as the little mutation [5].
• GHRH receptor of little mice contains a missense mutation in the extracellular domain that disrupts receptor function [5].
• Expression of GHRH and splice variant 1 of the GHRH receptor in both cell lines was examined by RT-PCR [6].
• Although GHRH and its receptor (GHRHR) are expressed in leukocytes, physiological function of GHRH in the immune system remains unclear [1].
• Splenocytes from MOG-immunized lit/lit mice proliferated normally in response to MOG peptide, suggesting that activation of MOG-specific T cells in GHRHR-deficient mice is not impaired [1].

Biological context of Ghrhr

• No recombinations between lit and Ghrfr were detected [7].
• The defect has been mapped to a missense mutation in the GHRH receptor gene that abolishes the function of the receptor, but the mechanism of this inactivation is unknown [8].
• The phenotype is strikingly similar to that observed in the mouse with mutated GHRH receptor (little) [9].
• Linkage analysis of microsatellite chromosomal markers near other candidate genes yielded a high LOD score (6.26) for the GHRH receptor (GHRH-R) locus [10].
• In addition, glucocorticoids are potent positive regulators of GHRH receptor gene expression [11].

Anatomical context of Ghrhr

• By Western blot, GHRH-receptor in pituitary membranes from KO mice was reduced to 46% of the level found in wildtype (WT) mice (P=0.016) [12].
• In the mammary gland of growth hormone releasing hormone receptor mutant (Ghrhrlit/Ghrhrlit) mice, the MDGI gene was overexpressed [13].
• The rat GHRH receptor is expressed predominantly in the pituitary gland and in somatotroph cells [11].
• CONCLUSION: We describe significant hypoplasia of the adenohypophysis occurring in four dwarfs with a nonsense mutation in the GHRH receptor [14].

Associations of Ghrhr with chemical compounds

• Hexarelin (and probably other GHRPs) are not effective agents for the treatment of patients with GHRH resistance due to GHRH receptor deficiency [15].

Other interactions of Ghrhr

• In addition, treating primary pituitary cell cultures from lean mice with insulin reduced GH release as well as GH, GHRH receptor, and ghrelin receptor mRNA levels compared with vehicle-treated controls, where the magnitude of suppression of pituitary mRNA levels was similar to that observed in the DIO mouse [16].

Analytical, diagnostic and therapeutic context of Ghrhr

• In this study, Western blots, using antiserum raised against the GHRH receptor and immunoprecipitation analysis of epitope-tagged receptors, demonstrate that both wild-type and mutant receptor proteins are expressed at equivalent levels in transfected cells [8].
• Alterations in EEG activity and sleep after influenza viral infection in GHRH receptor-deficient mice [17].

References