title: Significance of neonatal testicular sex steroids to defeminize anteroventral periventricular kisspeptin neurons and the GnRH/LH surge system in male rats.
abstract: The brain mechanism regulating gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) release is sexually differentiated in rodents. Kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) have been suggested to be sexually dimorphic and involved in the GnRH/LH surge generation. The present study aimed to determine the significance of neonatal testicular androgen to defeminize AVPV kisspeptin expression and the GnRH/LH surge-generating system. To this end, we tested whether neonatal castration feminizes AVPV kisspeptin neurons and the LH surge-generating system in male rats and whether neonatal estradiol benzoate (EB) treatment suppresses the kisspeptin expression and the LH surge in female rats. Immunohistochemistry, in situ hybridization, and quantitative real-time RT-PCR were performed to investigate kisspeptin and Kiss1 mRNA expressions. Male rats were castrated immediately after birth, and females were treated with EB on postnatal Day 5. Neonatal castration caused an increase in AVPV kisspeptin expression at peptide and mRNA levels in the genetically male rats, and the animals showed surge-like LH release in the presence of the preovulatory level of estradiol (E2) at adulthood. On the other hand, neonatal EB treatment decreased the number of AVPV kisspeptin neurons and caused an absence of E2-induced LH surge in female rats. Semiquantitative RT-PCR analysis showed that neonatal steroidal manipulation affects Kiss1 expression but does not significantly affect gene expressions of neuropeptides (neurotensin and galanin) and enzymes or transporter for neurotransmitters (gamma-aminobutyric acid, glutamate, and dopamine) in the AVPV, suggesting that the manipulation specifically affects Kiss1 expressions. Taken together, our present results provide physiological evidence that neonatal testicular androgen causes the reduction of AVPV kisspeptin expression and failure of LH surge in genetically male rats. Thus, it is plausible that perinatal testicular androgen causes defeminization of the AVPV kisspeptin system, resulting in the loss of the surge system in male rats.
authors.affiliation: Laboratory of Reproductive Science, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Tamami
authors.initials: T
authors.lastname: Homma
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Sakakibara
authors.forename: Shunji
authors.initials: S
authors.lastname: Yamada
authors.forename: Mika
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Kinuyo
authors.initials: K
authors.lastname: Iwata
authors.forename: Junko
authors.initials: J
authors.lastname: Tomikawa
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Kanazawa
authors.forename: Hisanori
authors.initials: H
authors.lastname: Matsui
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takatsu
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ohtaki
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Uenoyama
authors.forename: Kei-Ichiro
authors.initials: K
authors.lastname: Maeda
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tsukamura
mesh_terms: D000704:Analysis of Variance; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D004298:Dopamine / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D019004:Galanin / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D018698:Glutamic Acid / Q000235:genetics / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D059648:Kisspeptins; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009496:Neurotensin / Q000235:genetics / Q000378:metabolism; D009919:Orchiectomy; D010052:Ovariectomy; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012733:Sex Differentiation / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000235:genetics / Q000378:metabolism
chemical_list: D000728:Androgens; C491406:Kiss1 protein, rat; D059648:Kisspeptins; D011506:Proteins; D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D009496:Neurotensin; D018698:Glutamic Acid; D004958:Estradiol; D005680:gamma-Aminobutyric Acid; D019004:Galanin; D007986:Luteinizing Hormone; D004298:Dopamine