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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kamohara, Masazumi Nagano, Mamoru Naito, Masanori Takasaki, Jun Matsumoto, Shun-ichiro Hiyama, Hideki Ishii, Hiroyuki Furuichi, Kiyoshi Matsumoto, Mitsuyuki Masumoto, Koh-hei Matsuo, Ayako Matsushime, Hitoshi Yamazaki, Chihiro Katoh, Masao Shigeyoshi, Yasufumi Soga, Takatoshi Kobori, Masato |
| Description | Author Affiliation: Matsumoto S ( Molecular Medicine Research Laboratories, Drug Discovery Research, Astellas Pharma, Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. shunichiro.matsumoto@jp.astellas.com); |
| Abstract | Prokineticins, multifunctional secreted proteins, activate two endogenous G protein-coupled receptors PKR1 and PKR2. From in situ 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 (Pkr1(-/-) and Pkr2(-/-), respectively). Phenotypic analysis indicated that not Pkr1(-/-)but Pkr2(-/-)mice exhibited hypoplasia of the OB. This abnormality was observed in the early developmental stages of fetal OB in the Pkr2(-/-) mice. In addition, the Pkr2(-/-) mice showed severe atrophy of the reproductive system, including the testis, ovary, uterus, vagina, and mammary gland. In the Pkr2(-/-) 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 Pkr2(-/-) mice. The phenotype of the Pkr2(-/-) 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 11 |
| Volume Number | 103 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2006-03-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Gastrointestinal Hormones Metabolism Genitalia Abnormalities Neuropeptides Olfactory Bulb Receptors, G-Protein-Coupled Deficiency Receptors, Peptide Animals Gonadotropin-Releasing Hormone Genetics Kallmann Syndrome Etiology Mice Mice, Inbred C57BL Mice, Knockout Neurons Pregnancy RNA, Messenger Sexual Maturation Physiology Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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