Involvement of anteroventral periventricular metastin/kisspeptin neurons in estrogen positive feedback action on luteinizing hormone release in female rats.
Metastin/kisspeptin, the KiSS-1 gene product, has been identified as an endogenous ligand of GPR54 that reportedly regulates GnRH/LH surges and estrous cyclicity in female rats. The aim of the present study was to determine if metastin/kisspeptin neurons are a target of estrogen positive feedback to induce GnRH/LH surges. We demonstrated that preoptic area (POA) infusion of the anti-rat metastin/kisspeptin monoclonal antibody blocked the estrogen-induced LH surge, indicating that endogenous metastin/kisspeptin released around the POA mediates the estrogen positive feedback effect on GnRH/LH release. Metastin/kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) may be responsible for mediating the feedback effect because the percentage of c-Fos-expressing KiSS-1 mRNA-positive cells to total KiSS-1 mRNA-positive cells was significantly higher in the afternoon than in the morning in the anteroventral periventricular nucleus (AVPV) of high estradiol (E(2))-treated females. The percentage of c-Fos-expressing metastin/kisspeptin neurons was not different between the afternoon and morning in the arcuate nucleus (ARC). Most of the KiSS-1 mRNA expressing cells contain ERalpha immunoreactivity in the AVPV and ARC. In addition, AVPV KiSS-1 mRNA expressions were highest in the proestrous afternoon and lowest in the diestrus 1 in females and were increased by estrogen treatment in ovariectomized animals. On the other hand, the ARC KiSS-1 mRNA expressions were highest at diestrus 2 and lowest at proestrous afternoon and were increased by ovariectomy and decreased by high estrogen treatment. Males lacking the surge mode of GnRH/LH release showed no obvious cluster of metastin/kisspeptin-immunoreactive neurons in the AVPV when compared with high E(2)-treated females, which showed a much greater density of these neurons. Taken together, the present study demonstrates that the AVPV metastin/kisspeptin neurons are a target of estrogen positive feedback to induce GnRH/LH surges in female rats.
Adachi
Sachika
S
Graduate School of Science and Engineering, Saitama University, Saitama, Japan.
Yamada
Shunji
S
Takatsu
Yoshihiro
Y
Matsui
Hisanori
H
Kinoshita
Mika
M
Takase
Kenji
K
Sugiura
Hitomi
H
Ohtaki
Tetsuya
T
Matsumoto
Hirokazu
H
Uenoyama
Yoshihisa
Y
Tsukamura
Hiroko
H
Inoue
Kinji
K
Maeda
Kei-Ichiro
K
D000818:Animals; D020643:Anterior Thalamic Nuclei / Q000187:drug effects / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000008:administration & dosage; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000235:genetics; D004967:Estrogens / Q000378:metabolism*; D030762:Estrous Cycle / Q000502:physiology; D025461:Feedback, Physiological; D005260:Female; D005786:Gene Expression Regulation; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D059648:Kisspeptins; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D011301:Preoptic Area / Q000187:drug effects; D011506:Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000235:genetics; D000074502:Receptors, Kisspeptin-1
D000911:Antibodies, Monoclonal; D047628:Estrogen Receptor alpha; D004967:Estrogens; C491406:Kiss1 protein, rat; C492247:Kiss1r protein, rat; D059648:Kisspeptins; D011506:Proteins; D016760:Proto-Oncogene Proteins c-fos; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone