Open AccessAbnormal development of the olfactory bulb and reproductive system in mice lacking prokineticin receptor PKR2
Author(s) -
S. Matsumoto,
C. Yamazaki,
Kouji Masumoto,
Mamoru Nagano,
Masanori Naito,
Tsunehiko Soga,
Hideki Hiyama,
Mitsuyuki Matsumoto,
Jun Takasaki,
Masazumi Kamohara,
Ayako Matsuo,
Hiroyuki Ishii,
Masato Kobori,
Miyuki Katoh,
Hitoshi Matsushime,
Kiyoshi Furuichi,
Yasufumi Shigeyoshi
Publication year - 2006
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0508881103
Subject(s) - endocrinology , medicine , biology , hypogonadotropic hypogonadism , hypothalamus , luteinizing hormone , hormone
Prokineticins, multifunctional secreted proteins, activate two endogenous G protein-coupled receptors PKR1 and PKR2. Fromin 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 −/− andPkr2 −/− , respectively). Phenotypic analysis indicated that notPkr1 −/− butPkr2 −/− mice exhibited hypoplasia of the OB. This abnormality was observed in the early developmental stages of fetal OB in thePkr2 −/− mice. In addition, thePkr2 −/− mice showed severe atrophy of the reproductive system, including the testis, ovary, uterus, vagina, and mammary gland. In thePkr2 −/− 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 thePkr2 −/− mice. The phenotype of thePkr2 −/− 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.