{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:16:32Z","timestamp":1791900992361,"version":"4.3.4"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"11","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,3,14]]},"abstract":"<jats:p>\n                    Prokineticins, multifunctional secreted proteins, activate two endogenous G protein-coupled receptors PKR1 and PKR2. From\n                    <jats:italic>in situ<\/jats:italic>\n                    analysis of the mouse brain, we discovered that PKR2 is predominantly expressed in the olfactory bulb (OB). To examine the role of PKR2 in the OB, we created PKR1- and PKR2-gene-disrupted mice (\n                    <jats:italic>Pkr1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    and\n                    <jats:italic>Pkr2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    , respectively). Phenotypic analysis indicated that not\n                    <jats:italic>Pkr1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    but\n                    <jats:italic>Pkr2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice exhibited hypoplasia of the OB. This abnormality was observed in the early developmental stages of fetal OB in the\n                    <jats:italic>Pkr2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. In addition, the\n                    <jats:italic>Pkr2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice showed severe atrophy of the reproductive system, including the testis, ovary, uterus, vagina, and mammary gland. In the\n                    <jats:italic>Pkr2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, the plasma levels of testosterone and follicle-stimulating hormone were decreased, and the mRNA transcription levels of gonadotropin-releasing hormone in the hypothalamus and luteinizing hormone and follicle-stimulating hormone in the pituitary were also significantly reduced. Immunohistochemical analysis revealed that gonadotropin-releasing hormone neurons were absent in the hypothalamus in the\n                    <jats:italic>Pkr2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. The phenotype of the\n                    <jats:italic>Pkr2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice showed similarity to the clinical features of Kallmann syndrome, a human disease characterized by association of hypogonadotropic hypogonadism and anosmia. Our current findings demonstrated that physiological activation of PKR2 is essential for normal development of the OB and sexual maturation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0508881103","type":"journal-article","created":{"date-parts":[[2006,3,2]],"date-time":"2006-03-02T20:45:25Z","timestamp":1141332325000},"page":"4140-4145","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":235,"title":["Abnormal development of the olfactory bulb and reproductive system in mice lacking prokineticin receptor PKR2"],"prefix":"10.1073","volume":"103","author":[{"given":"Shun-ichiro","family":"Matsumoto","sequence":"first","affiliation":[{"name":"*Molecular Medicine Research Laboratories, Drug Discovery Research, Astellas Pharma, Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, 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589-8511, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Naito","sequence":"additional","affiliation":[{"name":"*Molecular Medicine Research Laboratories, Drug Discovery Research, Astellas Pharma, Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takatoshi","family":"Soga","sequence":"additional","affiliation":[{"name":"*Molecular Medicine Research Laboratories, Drug Discovery Research, Astellas Pharma, Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Hiyama","sequence":"additional","affiliation":[{"name":"*Molecular Medicine Research Laboratories, Drug Discovery Research, Astellas Pharma, Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, 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