{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe prolactin‐releasing peptide receptor (PRLHR, also known as GPR10) is a G protein‐coupled receptor that mediates the bioactivity of prolactin‐releasing peptide in diverse tissues. Aberrant activation of PRLHR is implicated in the pathogenesis of uterine fibroids (leiomyomas) through stimulation of the PI3K–AKT–mTOR pathway, and its expression is tightly controlled by transcriptional repressors such as REST to maintain normal cellular growth. In addition, enhanced receptor expression in endocrine tissues, as observed in pituitary adenomas and pheochromocytomas, supports a role in tumor biology and cell proliferation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in tumorigenesis, PRLHR is centrally involved in regulating energy homeostasis, appetite, and blood pressure. Genetic studies have uncovered rare receptor variants that impair ligand binding and G protein–dependent signaling, leading to altered feeding behavior, diminished energy expenditure, and modified blood pressure responses to physical activity. Detailed receptor mutagenesis and structure–function analyses have identified key amino acid residues critical for the ligand–receptor interaction, highlighting the challenges in designing selective RF‐amide peptide analogues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nExpanding its clinical significance, genetic association studies have linked polymorphisms in the PRLHR gene to increased risks for certain malignancies, including gastric and colorectal cancers, suggesting that altered receptor function may contribute to oncogenic processes across organ systems."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Atsushi Ozawa, Masanobu Yamada, Teturou Satoh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "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."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/mend.16.4.0819"}], "href": "https://doi.org/10.1210/mend.16.4.0819"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11923475"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11923475"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kazuhiro Takahashi, Kazuhito Totsune, Osamu Murakami, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of prolactin-releasing peptide and its receptor in the human adrenal glands and tumor tissues of adrenocortical tumors, pheochromocytomas and neuroblastomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Peptides (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0196-9781(02)00046-3"}], "href": "https://doi.org/10.1016/s0196-9781(02"}, {"type": "t", "text": "00046-3) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12126742"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12126742"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Daniel M Kemp, Julia C Lin, Mariano Ubeda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NRSF/REST confers transcriptional repression of the GPR10 gene via a putative NRSE/RE-1 located in the 5' promoter region."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0014-5793(02)03502-0"}], "href": "https://doi.org/10.1016/s0014-5793(02"}, {"type": "t", "text": "03502-0) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12417311"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12417311"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Binny V Varghese, Faezeh Koohestani, Michelle McWilliams, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "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."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/diabetes.52.5.1296"}], "href": "https://doi.org/10.2337/diabetes.52.5.1296"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12716769"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12716769"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Paul W Franks, Sumit Bhattacharyya, Jian'an Luan, et al. 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