The role of kisspeptin and RFRP-3 in the neuroendocrine control of female reproduction

Kisspeptin 和 RFRP-3 在女性生殖神经​​内分泌控制中的作用

• 批准号: 10377494
• 负责人: Lance J Kriegsfeld
• 金额: $ 42.66万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10377494
• 关键词: Address; Anterior Hypothalamus; Biological; Birds; Brain; Cell Nucleus; Cells; Communication; Contraceptive methods; Cre driver; Data; Delayed Puberty; Development; Elements; Endocrine; Equilibrium; Estradiol; Estrogens; Estrous Cycle; Estrus; Event; Exhibits; Exposure to; Feedback; Female; Fertility; GNRH1 gene; Genes; Gonadotropin Hormone Releasing Hormone; Gonadotropins; Health; Hormonal; Hormones; Human; Individual; Infertility; KISS1 gene; Knowledge; Light; LoxP-flanked allele; Luteinizing Hormone; Maintenance; Mediating; Menstrual cycle; Modeling; Molecular; Mus; Neuroendocrine Cell; Neurons; Neuropeptides; Neurosecretory Systems; Orthologous Gene; Output; Ovulation; Pathway interactions; Peptides; Phenotype; Physiological; Polycystic Ovary Syndrome; Precocious Puberty; Pregnancy; Process; Proestrus; Progesterone; Publishing; Reproduction; Reproductive Biology; Reproductive Health; Rodent Control; Role; Signal Pathway; Signal Transduction; Sleep disturbances; Spontaneous abortion; System; Testing; Time; Transgenic Mice; Viral; Woman; Work; arginylphenylalaninamide; circadian; circadian pacemaker; designer receptors exclusively activated by designer drugs; disorder prevention; estrogenic; experience; insight; knock-down; mouse model; neurochemistry; novel; pregnancy failure; relating to nervous system; reproductive axis; reproductive function; reproductive system disorder; sleep pattern; small hairpin RNA; suprachiasmatic nucleus; tool; translational impact

Project Summary Successful female reproduction requires the precise temporal coordination of numerous neuroendocrine events by a master circadian pacemaker in the suprachiasmatic nucleus (SCN). Across species, including humans, disruptions to circadian timing result in pronounced abnormalities in the estrous/menstrual cycle, reductions in fertility, and increased miscarriage rates. Our findings to date provide evidence for a network of ovulatory control in which the SCN temporally coordinates the activity of two, key neuropeptidergic systems with opposing actions, the RFamide-related peptide-3 (RFRP-3, the mammalian ortholog of avian gonadotropin-inhibitory hormone) and kisspeptin systems. Across mammalian species, RFRP-3 and kisspeptin are key inhibitory and stimulatory regulators of the reproductive axis, respectively. Despite the well-established role for these neuropeptides in mammalian reproduction, as well as the knowledge that the circadian timing system is a crucial regulator of the female reproductive axis, the specific means by which interactions among these systems appropriately coordinate the timing of neuroendocrine events necessary for ovulation remain unspecified. To understand how elements of this network synergize to produce the coordinated output to the gonadotropin-releasing hormone (GnRH) system required for ovulation, the present proposal uses transgenic mouse models, in combination with cell-specific viral approaches, to elucidate the cellular mechanisms and neurochemical signaling pathways by which the circadian clockwork interfaces with the RFRP-3 and Kp systems. Specifically, the present proposal will: 1) identify the neurochemical signaling pathways by which the SCN communicates with the RFRP-3 and kisspeptin systems, 2) examine the functional contribution of identified pathways systematically, and with cell-specific precision, and 3) determine the functional significance of autonomous, neuroendocrine-cell circadian timekeeping in this network of control through cell-phenotype-specific knockdown of essential clock genes. The proposed work not only addresses a classic question in reproductive biology, but also has the potential for substantial translational impact in the development of safe/effective contraception, as well as the treatment of a host of reproductive disorders in humans, including precocious and delayed puberty, infertility, and polycystic ovarian syndrome.

项目总结

项目成果

Dorsomedial hypothalamic lesions counteract decreases in locomotor activity in male Syrian hamsters transferred from long to short day lengths.

• DOI: 10.1177/0748730414561546
• 发表时间: 2015-02
• 期刊: Journal of biological rhythms
• 影响因子: 3.5
• 作者: Jarjisian SG;Butler MP;Paul MJ;Place NJ;Prendergast BJ;Kriegsfeld LJ;Zucker I
• 通讯作者: Zucker I

Photoperiod and reproductive condition are associated with changes in RFamide-related peptide (RFRP) expression in Syrian hamsters (Mesocricetus auratus).

• DOI: 10.1177/0748730410368821
• 发表时间: 2010-06
• 期刊: Journal of biological rhythms
• 影响因子: 3.5
• 作者: Mason AO;Duffy S;Zhao S;Ubuka T;Bentley GE;Tsutsui K;Silver R;Kriegsfeld LJ
• 通讯作者: Kriegsfeld LJ

RFamide-related Peptide-3 and the Trade-off between Reproductive and Ingestive Behavior.

RFamide 相关肽 3 以及生殖行为和摄食行为之间的权衡。

• DOI: 10.1093/icb/icx097
• 发表时间: 2017
• 期刊: Integrative and comparative biology
• 影响因子: 2.6
• 作者: Schneider,JillE;Benton,NoahA;Russo,KimA;Klingerman,CandiceM;Williams3rd,WilburP;Simberlund,Jessica;Abdulhay,Amir;Brozek,JeremyM;Kriegsfeld,LanceJ
• 通讯作者: Kriegsfeld,LanceJ

Effects of Pinealectomy and Short Day Lengths on Reproduction and Neuronal RFRP-3, Kisspeptin, and GnRH in Female Turkish Hamsters.

• DOI: 10.1177/0748730414532423
• 发表时间: 2014-06
• 期刊: Journal of biological rhythms
• 影响因子: 3.5
• 作者: Piekarski DJ;Jarjisian SG;Perez L;Ahmad H;Dhawan N;Zucker I;Kriegsfeld LJ
• 通讯作者: Kriegsfeld LJ

Maternal programming of sexual attractivity in female Long Evans rats.

• DOI: 10.1016/j.psyneuen.2011.02.016
• 发表时间: 2011-09
• 期刊: PSYCHONEUROENDOCRINOLOGY
• 影响因子: 3.7
• 作者: Sakhai, Samuel A.;Kriegsfeld, Lance J.;Francis, Darlene D.
• 通讯作者: Francis, Darlene D.