Disease relevance of PRLH

• In contrast, PrRP mRNA was detected in only 5 of 11 of the human prolactinomas [1].
• Using RT-PCR, we examined messenger ribonucleic acid (mRNA) expression of PrRP and its receptor in normal human pituitary tissue and in pituitary tumors [1].
• The high expression of PrRP receptor in pheochromocytomas suggests potential pathophysiological roles of PrRP in these tumors [2].
• Immunoreactive-PrRP was detected in normal portions of adrenal glands (0.162+/-0.024 pmol/g wet weight, n=4, mean+/-S.E.M.), four out of six cases of pheochromocytomas (0.050-7.9 pmol/g wet weight), one neuroblastoma and some adrenocortical tumors [2].
• Here we show a reduction in the expression of PrRP mRNA during lactation and fasting and an acute effect of PrRP on food intake and body weight, supporting the hypothesis of an alternative role for the peptide [3].

High impact information on PRLH

• 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 [4].
• Prolactin-releasing peptide (PrRP) and its G-protein-coupled receptor, GPR10, have been implicated in the central control of appetite and blood pressure [4].
• A fragment of PRH that includes the homeodomain can bind to TATA box sequences in vitro and can also bind to the TATA box-binding protein [5].
• Oligomerisation of the Developmental Regulator Proline Rich Homeodomain (PRH/Hex) is Mediated by a Novel Proline-rich Dimerisation Domain [6].
• PrRP enhanced GH release in several GH-secreting adenomas studied by 25--27%, including GH stimulation in a mixed PRL-GH-cell tumor [7].

Chemical compound and disease context of PRLH

• All 5 prolactinomas expressing PrRP were responsive to dopamine agonist treatment, whereas PrRP-negative prolactinomas were non- or partially responsive [1].
• Isolated adult human keratinocytes were grown either on plastic coverslips or a nonviable basement membrane surface containing intact laminin, type IV and V collagens, and heparan sulfate proteoglycan and examined by indirect immunofluorescence for the expression of bullous pemphigoid, pemphigus and Prlh antigens [8].

Biological context of PRLH

• PrRP gene expression was detected in both the placenta and decidua [9].
• In conclusion, we have conducted the first genetic study of GPR10 and its ligand PrRP in relation to metabolic phenotypes and have identified an association between GPR10 polymorphisms and diastolic and systolic blood pressure [4].
• 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 [10].
• One of our clones was found to encode a protein with 90% amino acid identity to human GPR10, which was previously identified as the receptor for prolactin-releasing peptide (PrRP) and has been implicated in lactation, the regulation of food intake and other physiological functions [11].
• PRH represses transcription from TATA box-containing promoters in intact cells but does not repress transcription from a promoter lacking a TATA box [5].

Anatomical context of PRLH

• PrRP mRNA was expressed in all five normal pituitary glands examined [1].
• The presence of immunoreactive-PrRP in the adrenal glands and in these tumor tissues was studied by radioimmunoassay [2].
• To determine whether PrRP affects decidual PRL secretion, human endometrial stromal cells and decidual cells were cultured and treated with or without 1 microM PrRP31 [9].
• 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].
• Tissue specimens were stained by immunohistochemistry using a rabbit anti-human PrRP-31 antibody, and PrRP was localized in both epithelial cells of the decidual glands and in stromal cells, with diffuse distribution and no special relation with the neighbourhood of blood vessels [13].

Associations of PRLH with chemical compounds

• PrRP may thus signal through the NPFF receptors in vivo [14].
• Peptide histidine methionine may be a prolactin-releasing hormone in humans [15].
• Coincubation with estradiol resulted in enhanced fetal PRL response to PrRP, and GH release was only increased in the presence of estradiol [7].
• Sodium tanshinone IIA sulfonate derived from Slavia miltiorrhiza Bunge up-regulate the expression of prolactin releasing peptide (PrRP) in the medulla oblongata in ovariectomized rats [16].
• Intracerebroventricular injection of neutralizing anti-PrRP antibodies led to increased plasma ACTH level and blood lactate accumulation during running stress, but not during restraint stress [17].

Physical interactions of PRLH

• Moreover, a micromolar level of NPY was able to bind and inhibit completely the PRLH-evoked response in PRLHR1-expressing cells [18].

Regulatory relationships of PRLH

• The recently identified PRL-releasing peptide (PrRP) is the first hypothalamic peptide hormone that specifically stimulates PRL production from the pituitary gland [1].

Other interactions of PRLH

• We suggest that an ancestral PRLH peptide started coevolving with a redundant NPY binding receptor, which then became PRLHR, approximately 500 million years ago [18].
• Further investigation of PrRP and its receptor expression and function will be needed to clarify its potential role in regulating PRL secretion in normal human lactotrophs and pituitary tumors [1].
• Growth hormone-, beta-thyroid-stimulating hormone-, beta-follicle-stimulating hormone-, beta-luteinizing hormone- or alpha-subunit-positive cells did not test positive for the presence of PrRP receptors [19].
• The affinity and functional activity of several related RFamide peptides were determined at the human neuropeptide FF receptor subtype 2 (hNPFF2) and the human prolactin-releasing peptide (hPrRP) receptors [14].

Analytical, diagnostic and therapeutic context of PRLH

• These results suggest that the mechanism that STS improved postmenopausal symptoms induced by ovariectomy in rats might be related to the modulation of the blood E2 level and the expression of PrRP in medulla oblongata of ovariectomized rats [16].
• Electroacupuncture stimulates the expression of prolactin-releasing peptide (PrRP) in the medulla oblongata of ovariectomized rats [20].
• The putative PrRP was purified from an acid extract of tilapia brain by affinity chromatography with antibody against synthetic C-RFa and HPLC on a reverse-phase ODS-120 column [21].

References