title: Kisspeptin neurons in the ovine arcuate nucleus and preoptic area are involved in the preovulatory luteinizing hormone surge.
abstract: Kisspeptin is the product of the Kiss1 gene that regulates GnRH secretion. In sheep, Kiss1 mRNA-expressing cells are found in the preoptic area (POA) and arcuate nucleus (ARC), and expression is up-regulated in the caudal ARC during the periovulatory period. We hypothesized that kisspeptin neurons in the ARC are activated by estradiol-17beta prior to the preovulatory LH surge. Ovariectomized ewes were treated as follows: 1) estradiol-17beta implants (sc 2 wk) to cause tonic negative feedback; 2) vehicle (no estrogen negative or positive feedback); or 3) positive feedback/GnRH surge-inducing injection of estradiol-17beta (50 microg iv). For groups 2 and 3, brains were collected 1 h after treatment and kisspeptin/Fos immunoreactivity was examined. In the caudal and mid-ARC, the percentage of kisspeptin cells that were Fos immunoreactive increased after acute estradiol treatment (group 3) over that seen in the other two groups. Kisspeptin/Fos colocalization was also quantified in ewes during the luteal and late-follicular phase of the estrous cycle, showing a trend toward an increase in colocalization in the late-follicular phase. Kisspeptin/Fos colocalization was similar in the POA across groups in both experiments. Analysis of Kiss1 mRNA by in situ hybridization revealed an increase in expression during the late-follicular phase in the caudal ARC and POA. These data suggest kisspeptin neurons located in the caudal extent of the ARC are involved in generating the positive feedback preovulatory GnRH/LH surge in the ewe, but there may also be a role for Kiss1-expressing cells in the POA.
authors.affiliation: Department of Physiology, Monash University, Clayton, Victoria 3880, Australia. jeremy.smith@med.monash.edu.au
authors.forename: J T
authors.initials: JT
authors.lastname: Smith
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: A
authors.initials: A
authors.lastname: Pereira
authors.forename: I J
authors.initials: IJ
authors.lastname: Clarke
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D030762:Estrous Cycle; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010052:Ovariectomy; D010060:Ovulation; D011301:Preoptic Area / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012756:Sheep; D013997:Time Factors; D015533:Transcriptional Activation / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004967:Estrogens; D016760:Proto-Oncogene Proteins c-fos; D025521:Tumor Suppressor Proteins; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone