Disease relevance of PRLHR

• To examine whether genetic variation of the GPR10 locus might be associated with phenotypes relevant to obesity and/or blood pressure, the most common noncoding (G-62A) and coding (C914T [P305L]) polymorphisms were typed in 1,084 U.K. Caucasians [1].
• PRL-releasing peptide receptor (PrRPR) mRNA was expressed in pituitary adenomas but was not detected in patients treated with bromocriptine, a specific agonist of dopamine 2 (D2) receptor [2].
• In the present study, expression of PrRP receptor was studied in the human brain, pituitaries, adrenal glands and tumor tissues of adrenocortical tumors, pheochromocytomas, a ganglioneuroblastoma and neuroblastomas by reverse transcriptase polymerase chain reaction (RT-PCR) and Northern blot analysis [3].
• Second, we investigated the effect of normal and high-fat diets on energy intake, body weight, and glucose homeostasis in wild-type and GPR10 knockout mice [4].
• In addition, the latter molecule supported the growth of the G-CSF dependent cell line FD/GR3, which is a murine myeloid leukemia cell line, FDC-P2, transfected with mG-CSF receptor cDNA [5].

Psychiatry related information on PRLHR

• Association between physical activity and blood pressure is modified by variants in the G-protein coupled receptor 10 [6].

High impact information on PRLHR

• We then searched for the hGR3 ligand in the hypothalamus and identified a new peptide, which shares no sequence similarity with known peptides and proteins, as an endogenous ligand [7].
• Four rare silent variants in PrRP and eight polymorphisms in GPR10 were found, two of which (V283I and P305L) altered amino acid sequence but were also found in U.K. Caucasian control subjects [1].
• Association of polymorphisms in GPR10, the gene encoding the prolactin-releasing peptide receptor with blood pressure, but not obesity, in a U.K. Caucasian population [1].
• Therefore, the transcriptional repression of the PrRPR gene by bromocriptine required CREB but was independent of direct binding of CREB to the gene and that the sequence -663 -- -672, 5'-cccacatcat-3', bound to the 60-kDa protein appeared to be critical for this event [2].
• Transcriptional regulation of the human PRL-releasing peptide (PrRP) receptor gene by a dopamine 2 Receptor agonist: cloning and characterization of the human PrRP receptor gene and its promoter region [2].

Biological context of PRLHR

• The cloned human PrRPR gene spanned approximately 2.0 kb and contained two exons and one intron [2].
• Fluorescence in situ hybridization analysis localized GPR9 to chromosome 8p11.2-p12 and GPR10 to chromosome 10q25.3-q26 [8].
• To evaluate the regulation of human (h) PrRP-receptor (PrRP-R) gene expression, we cloned the 5'-flanking region of the hPrRP-R gene and determined the nucleotide sequence of 4.0 kilobase pairs (kb) upstream from the translation start site [9].
• Analysis of the hPrRP-R transcripts by means of 5'-rapid amplification of cDNA ends suggested that the hPrRP-R gene had multiple transcription start sites between -429 and -365 from the translation start site [9].
• These results suggest that the plasma prolactin level is regulated by means other than signal transduction through PrRP-R activation [10].

Anatomical context of PRLHR

• In contrast, in the GPR10-expressing cell line GH3, mRNA transcripts of NRSF were undetectable and suppression of promoter activity was not observed [11].
• The present study has shown that PrRP receptor mRNA was widely expressed in the brain tissues, pituitaries, adrenal glands and various tumors [3].
• Such PrRP analogues could be useful receptorial tools able to clarify the multiple biological functions hypothesized for the PrRP receptor in the central nervous system [12].
• In primary cultures of decidual stromal cells, PrRP and PrRP receptor gene expression were detected using RT-PCR, and the identity of the PCR products was further confirmed by restriction enzyme digestion [13].
• A double immunohistochemical procedure was used to examine PrRP receptor-positive cells from ten normal human pituitary glands, and it was determined that numerous PrRP receptor-positive cells are also positive for adrenocorticotropic hormone (ACTH) but negative for PRL [14].

Associations of PRLHR with chemical compounds

• None of the drugs tested, including the RF-amide neuropeptide FF, demonstrated any affinity for GPR10 [15].
• Human PrRP-20 failed to alter basal or forskolin-stimulated levels of intracellular cyclic AMP in HEK293-GPR10 cells, suggesting that GPR10 does not couple via either G(s) or G(i) [15].

Regulatory relationships of PRLHR

• Does prolactin releasing peptide receptor regulate prolactin-secretion in human pituitary adenomas [10]?

Other interactions of PRLHR

• The high expression of PrRP receptor in pheochromocytomas suggests potential pathophysiological roles of PrRP in these tumors [3].
• GPR10 encodes a receptor that shares highest identity with the neuropeptide Y receptor (31% overall and 46% in the transmembrane domains) [8].
• Our study indicated a generally relatively low level of discrimination for RFamide peptides at the NPFF receptor, whereas the hPrRP receptor clearly preferred PrRP or very closely related peptides [16].

Analytical, diagnostic and therapeutic context of PRLHR

• RT-PCR analysis showed expression of PrRP receptor in the human brain, pituitaries, normal portions of adrenal glands and various tumor tissues [3].
• This is the first report to demonstrate colocalization of the PrRP receptor and ACTH by immunohistochemistry [14].

References