Review
Endocrinology & Metabolism
Bijal Patel, Kanyada Koysombat, Edouard G. Mills, Jovanna Tsoutsouki, Alexander N. Comninos, Ali Abbara, Waljit S. Dhillo
Summary: This review provides a comprehensive overview of the research on Kisspeptin (KP) and neurokinin B (NKB), two neuropeptides that regulate the reproductive endocrine axis. Their critical role in reproductive health has been identified, and research has shown their potential therapeutic applications in various disorders. The expression of KP and NKB in different tissues opens up avenues for research in pregnancy, metabolic, liver, bone, and behavioral disorders. Additionally, NKB antagonism has shown promise as a nonsteroidal therapeutic agent for menopausal hot flashes and reproductive disorders.
Article
Endocrinology & Metabolism
Steve Pawsey, Edouard Gregory Mills, Elizabeth Ballantyne, Kirsteen Donaldson, Mary Kerr, Mike Trower, Waljit Singh Dhillo
Summary: The study found that elinzanetant can lengthen the menstrual cycle by suppressing reproductive hormone levels such as luteinizing hormone and estradiol, and does not produce vasomotor symptoms during treatment.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Biology
Eliana G. Aerts, KaLynn Harlow, Max J. Griesgraber, Elizabeth C. Bowdridge, Steven L. Hardy, Casey C. Nestor, Stanley M. Hileman
Summary: The study found that kisspeptin and NKB expression levels were evident well before the pubertal increase in LH secretion and did not change with age, while dynorphin expression increased postpuberty. Despite the critical role of KNDy neurons in puberty, they may require inputs from other neural systems to trigger puberty onset.
Article
Multidisciplinary Sciences
Mayuko Nagae, Yoshihisa Uenoyama, Saki Okamoto, Hitomi Tsuchida, Kana Ikegami, Teppei Goto, Sutisa Majarune, Sho Nakamura, Makoto Sanbo, Masumi Hirabayashi, Kenta Kobayashi, Naoko Inoue, Hiroko Tsukamura
Summary: The study demonstrates that KNDy neurons serve as the GnRH pulse generator, and at least 20% of KNDy neurons are sufficient to maintain folliculogenesis. This provides a new therapeutic approach for treating infertile women.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Naoko Inoue, Safiullah Hazim, Hitomi Tsuchida, Yuri Dohi, Ren Ishigaki, Ai Takahashi, Yuki Otsuka, Koki Yamada, Yoshihisa Uenoyama, Hiroko Tsukamura
Summary: Ovulation in female rodents is triggered by ATP-purinergic signaling, which activates kisspeptin neurons in the AVPV. The administration of an ATP receptor antagonist blocks the LH surge and reduces ovulation rate. ATP also increases intracellular Ca2+ levels in kisspeptin neurons, indicating its role in mediating ovulation.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Endocrinology & Metabolism
Robert L. Goodman, Aleisha M. Moore, Kayla Onslow, Stanley M. Hileman, Steve L. Hardy, Elizabeth C. Bowdridge, Burgundy A. Walters, Sami Agus, Max J. Griesgraber, Eliana G. Aerts, Michael N. Lehman, Lique M. Coolen
Summary: This study found that KNDy neurons are essential for GnRH pulses in ewes, while ARC Kiss1R cells do not directly contribute to the generation of GnRH pulses but maintain their amplitude and regularity.
Article
Cell Biology
Anne Abot, Vincent Robert, Renaud Fleurot, Hugues Dardente, Vincent Hellier, Pascal Froment, Anne Duittoz, Claude Knauf, Laurence Dufourny
Summary: Hypothalamic control of reproduction relies on secretions of GnRH and kisspeptin (KP). This study found neuroanatomical contacts between apelin fibers and both KP and GnRH neurons in the hypothalamus of male rodents. Intracerebroventricular apelin infusion did not decrease LH levels nor affect gene expression for KP, neurokinin B, and dynorphin. However, apelin did affect the secretory activity of GnRH neurons.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Graeme L. Fraser, Barbara Obermayer-Pietsch, Joop Laven, Georg Griesinger, Axelle Pintiaux, Dirk Timmerman, Bart C. J. M. Fauser, Christopher Lademacher, Jean Combalbert, Hamid R. Hoveyda, Steven Ramael
Summary: This study evaluated the clinical efficacy and safety of the neurokinin 3 (NK3) receptor antagonist fezolinetant in women with PCOS. Fezolinetant was found to effectively suppress hyperandrogenism and reduce the LH-to-FSH ratio in a dose-dependent manner. The treatment was well tolerated by participants.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Multidisciplinary Sciences
Juan Roa, Miguel Ruiz-Cruz, Francisco Ruiz-Pino, Rocio Onieva, Maria J. Vazquez, Maria J. Sanchez-Tapia, Jose M. Ruiz-Rodriguez, Veronica Sobrino, Alexia Barroso, Violeta Heras, Inmaculada Velasco, Cecilia Perdices-Lopez, Claes Ohlsson, Maria Soledad Avendano, Vincent Prevot, Matti Poutanen, Leonor Pinilla, Francisco Gaytan, Manuel Tena-Sempere
Summary: Research shows that Kiss1 neurons play an essential role in puberty and fertility, and the miRNA biosynthesis in these neurons is crucial for the completion of puberty and fertility, especially in females.
NATURE COMMUNICATIONS
(2022)
Article
Environmental Sciences
Anna Szeliga, Ewa Rudnicka, Marzena Maciejewska-Jeske, Marek Kucharski, Anna Kostrzak, Marta Hajbos, Olga Niwczyk, Roman Smolarczyk, Blazej Meczekalski
Summary: PCOS, the most common endocrine disorder in women, is diagnosed based on the presence of two out of three clinical symptoms and is mainly regulated by neurohormones like GnRH. Studies have shown abnormalities in neuroendocrine regulation in PCOS patients, including rapid GnRH pulse frequency and elevated kisspeptin levels.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2022)
Review
Endocrinology & Metabolism
Akanksha Garg, Bijal Patel, Ali Abbara, Waljit S. Dhillo
Summary: PCOS is the most common endocrine disorder in women of reproductive age, and its increased GnRH pulsatility is caused by various factors. Targeting the activity of KNDy neurons using pharmaceutical agents is being researched as a potential method to alleviate symptoms of PCOS. Neurokinin 3 receptor antagonists show promise in reducing GnRH pulsatility and relieving PCOS symptoms.
CLINICAL ENDOCRINOLOGY
(2022)
Review
Endocrinology & Metabolism
Noemi Salmeri, Paola Vigano, Paolo Cavoretto, Roberto Marci, Massimo Candiani
Summary: Endometriosis and polycystic ovary syndrome (PCOS) are two common female reproductive disorders with opposite alterations in reproductive processes and phenotypic traits. Recent discovery of kisspeptin as a pivotal mediator in human reproduction and its involvement in metabolism, inflammation, and pain sensitivity provides new insights into understanding these conditions. This review discusses the clinical relevance and potential translational applications of these discoveries in developing novel therapies for endometriosis and PCOS.
REVIEWS IN ENDOCRINE & METABOLIC DISORDERS
(2023)
Review
Cell Biology
Virginia Delli, Mauro S. B. Silva, Vincent Prevot, Konstantina Chachlaki
Summary: Kisspeptin and nitric oxide play opposing roles in regulating GnRH secretion, with kisspeptin promoting release and NO inhibiting secretion, creating a dynamic interplay that is fine-tuned by the gonadal steroid environment.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2021)
Review
Endocrinology & Metabolism
Edouard G. Mills, Waljit S. Dhillo
Summary: This review focuses on the latest research on reproductive neuropeptides kisspeptin and neurokinin B, highlighting their potential applications in managing reproductive disorders.
JOURNAL OF NEUROENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Paul G. Morris, Allan E. Herbison
Summary: The synchronization of ARC kisspeptin neurons in female mice relies on glutamate signaling through AMPA receptors, with no involvement of NMDA receptors. Tachykinin receptor tone promotes spontaneous synchronizations in females. Dynorphin transmission does not contribute to synchronization events in females.
Article
Biochemistry & Molecular Biology
Mi Jin Moon, Yoo-Na Lee, Sumi Park, Arfaxad Reyes-Alcaraz, Jong-Ik Hwang, Robert Peter Millar, Han Choe, Jae Young Seong
JOURNAL OF BIOLOGICAL CHEMISTRY
(2015)
Article
Cell Biology
Nkateko M. I. Mayevu, Han Choe, Ruben Abagyan, Jae Young Seong, Robert P. Millar, Arieh A. Katz, Colleen A. Flanagan
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2015)
Editorial Material
Endocrinology & Metabolism
Robert P. Millar
NEUROENDOCRINOLOGY
(2015)
Article
Endocrinology & Metabolism
Robert P. Millar, Andy V. Babwah
NEUROENDOCRINOLOGY
(2015)
Article
Endocrinology & Metabolism
Qun Li, Robert P. Millar, Iain J. Clarke, Jeremy T. Smith
NEUROENDOCRINOLOGY
(2015)
Review
Microbiology
Ignatius M. Viljoen, Paul D. van Heiden, Robert P. Millar
VETERINARY MICROBIOLOGY
(2015)
Article
Endocrinology & Metabolism
Claire Louise Newton, Ross Calley Anderson, Arieh Anthony Katz, Robert Peter Millar
Article
Endocrinology & Metabolism
R. Pineda, N. Sabatier, M. Ludwig, R. P. Millar, G. Leng
JOURNAL OF NEUROENDOCRINOLOGY
(2016)
Article
Neurosciences
Joseph V. Raimondo, Hayley Tomes, Agnese Irkle, Louise Kay, Lauriston Kellaway, Henry Markram, Robert P. Millar, Colin J. Akerman
JOURNAL OF NEUROSCIENCE
(2016)
Article
Endocrinology & Metabolism
Rafael Pineda, Fabrice Plaisier, Robert P. Millar, Mike Ludwig
NEUROENDOCRINOLOGY
(2017)
Article
Oncology
Jesus A. Junco Barranco, Robert P. Millar, Franklin Fuentes, Eddy Bover, Eulogio Pimentel, Roberto Basulto, Lesvia Calzada, Rolando Moran, Ayni Rodriguez, Hilda Garay, Osvaldo Reyes, Maria D. Castro, Ricardo Bringas, Niurka Arteaga, Henio Touduri, Mauricio Rabassa, Yairis Fernandez, Andres Serradelo, Eduardo Hernandez, Gerardo E. Guillen
Article
Obstetrics & Gynecology
Mushi Matjila, Robert Millar, Zephne van der Spuy, Arieh Katz
PREGNANCY HYPERTENSION-AN INTERNATIONAL JOURNAL OF WOMENS CARDIOVASCULAR HEALTH
(2016)
Article
Endocrinology & Metabolism
Karolina Skorupskaite, Jyothis T. George, Johannes D. Veldhuis, Robert P. Millar, Richard A. Anderson
NEUROENDOCRINOLOGY
(2018)
Article
Endocrinology & Metabolism
J. T. George, M. Hendrikse, J. D. Veldhuis, I. J. Clarke, R. A. Anderson, R. P. Millar
CLINICAL ENDOCRINOLOGY
(2017)