title: Collapsin response mediator protein 4 affects the number of tyrosine hydroxylase-immunoreactive neurons in the sexually dimorphic nucleus in female mice.
abstract: In the sexually dimorphic anteroventral periventricular nucleus (AVPV) of the hypothalamus, females have a greater number of tyrosine hydroxylase-immunoreactive (TH-ir) and kisspeptin-immunoreactive (kisspeptin-ir) neurons than males. In this study, we used proteomics analysis and gene-deficient mice to identify proteins that regulate the number of TH-ir and kisspeptin-ir neurons in the AVPV. Analysis of protein expressions in the rat AVPV on postnatal day 1 (PD1; the early phase of sex differentiation) using two-dimensional fluorescence difference gel electrophoresis followed by MALDI-TOF-MS identified collapsin response mediator protein 4 (CRMP4) as a protein exhibiting sexually dimorphic expression. Interestingly, this sexually differential expressions of CRMP4 protein and mRNA in the AVPV was not detected on PD6. Prenatal testosterone exposure canceled the sexual difference in the expression of Crmp4 mRNA in the rat AVPV. Next, we used CRMP4-knockout (CRMP4-KO) mice to determine the in vivo function of CRMP4 in the AVPV. Crmp4 knockout did not change the number of kisspeptin-ir neurons in the adult AVPV in either sex. However, the number of TH-ir neurons was increased in the AVPV of adult female CRMP4-KO mice as compared with the adult female wild-type mice. During development, no significant difference in the number of TH-ir neurons was detected between sexes or genotypes on embryonic day 15, but a female-specific increase in TH-ir neurons was observed in CRMP4-KO mice on PD1, when the sex difference was not yet apparent in wild-type mice. These results indicate that CRMP4 regulates the number of TH-ir cell number in the female AVPV.
authors: Doctoral Program in Kansei, Behavioral and Brain Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8577, Japan.
authors: Takashi
authors: T
authors: Iwakura
authors: Miyuki
authors: M
authors: Sakoh
authors: Atsuhiro
authors: A
authors: Tsutiya
authors: Naoya
authors: N
authors: Yamashita
authors: Akiko
authors: A
authors: Ohtani
authors: Mumeko C
authors: MC
authors: Tsuda
authors: Sonoko
authors: S
authors: Ogawa
authors: Shinji
authors: S
authors: Tsukahara
authors: Masugi
authors: M
authors: Nishihara
authors: Takashi
authors: T
authors: Shiga
authors: Yoshio
authors: Y
authors: Goshima
authors: Tomohiro
authors: T
authors: Kato
authors: Ritsuko
authors: R
authors: Ohtani-Kaneko
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D005260:Female; D059648:Kisspeptins / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: C526904:Dpysl3 protein, mouse; C491407:Kiss1 protein, mouse; D059648:Kisspeptins; D009419:Nerve Tissue Proteins; D014446:Tyrosine 3-Monooxygenase