Robert P Millar

Summary

Affiliation: National Institute for Medical Research
Country: UK

Publications

  1. ncbi request reprint Gonadotropin-releasing hormone receptors
    Robert P Millar
    Medical Research Council Human Reproductive Sciences Unit, Centre for Reproductive Biology, Chancellor s Building, 49 Little France Crescent, Edinburgh EH16 4SB, Scotland, United Kingdom
    Endocr Rev 25:235-75. 2004
  2. ncbi request reprint GnRHs and GnRH receptors
    Robert P Millar
    MRC Human Reproductive Sciences Unit, The Chancellor s Building, 49 Little France Crescent, Edinburgh EH16 4SB, Scotland, UK
    Anim Reprod Sci 88:5-28. 2005
  3. pmc The year in G protein-coupled receptor research
    Robert P Millar
    Medical Research Council MRC Human Reproductive Sciences Unit, The Queen s Medical Research Institute, Edinburgh, Scotland, United Kingdom
    Mol Endocrinol 24:261-74. 2010
  4. pmc Kisspeptin signalling in the hypothalamic arcuate nucleus regulates GnRH pulse generator frequency in the rat
    Xiao Feng Li
    Division of Reproduction and Endocrinology, King s College London, London, United Kingdom
    PLoS ONE 4:e8334. 2009
  5. pmc A novel mammalian receptor for the evolutionarily conserved type II GnRH
    R Millar
    Medical Research Council Human Reproductive Sciences Unit, Edinburgh EH3 9ET, Scotland
    Proc Natl Acad Sci U S A 98:9636-41. 2001
  6. pmc Diversity of actions of GnRHs mediated by ligand-induced selective signaling
    Robert P Millar
    MRC Human Reproductive Sciences Unit, The Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
    Front Neuroendocrinol 29:17-35. 2008
  7. ncbi request reprint GnRH II and type II GnRH receptors
    Robert P Millar
    MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Chancellor s Building, 49 Little France Crescent, Old Dalkeith Road, Edinburgh EH16 4SB, UK
    Trends Endocrinol Metab 14:35-43. 2003
  8. pmc The chicken type III GnRH receptor homologue is predominantly expressed in the pituitary, and exhibits similar ligand selectivity to the type I receptor
    Nerine T Joseph
    Royal Dick School of Veterinary Studies, The Roslin Institute, University of Edinburgh, Roslin, Midlothian, Edinburgh, UK
    J Endocrinol 202:179-90. 2009
  9. pmc Transcript and protein profiling identifies signaling, growth arrest, apoptosis, and NF-κB survival signatures following GNRH receptor activation
    Colette Meyer
    Breakthrough Breast Cancer Research Unit and Division of Pathology, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road South, Edinburgh, UK
    Endocr Relat Cancer 20:123-36. 2013
  10. doi request reprint A crucial role for Galphaq/11, but not Galphai/o or Galphas, in gonadotropin-releasing hormone receptor-mediated cell growth inhibition
    Colin D White
    The Medical Research Council Human Reproductive Sciences Unit, The Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom
    Mol Endocrinol 22:2520-30. 2008

Detail Information

Publications76

  1. ncbi request reprint Gonadotropin-releasing hormone receptors
    Robert P Millar
    Medical Research Council Human Reproductive Sciences Unit, Centre for Reproductive Biology, Chancellor s Building, 49 Little France Crescent, Edinburgh EH16 4SB, Scotland, United Kingdom
    Endocr Rev 25:235-75. 2004
    ..Delineation of the structural elements in GnRH and the receptor, which facilitate differential signaling, will contribute to the development of novel interventive GnRH analogs...
  2. ncbi request reprint GnRHs and GnRH receptors
    Robert P Millar
    MRC Human Reproductive Sciences Unit, The Chancellor s Building, 49 Little France Crescent, Edinburgh EH16 4SB, Scotland, UK
    Anim Reprod Sci 88:5-28. 2005
    ..Together, these findings are setting the scene for generating novel selective GnRH analogues with potential for wider and more specific application...
  3. pmc The year in G protein-coupled receptor research
    Robert P Millar
    Medical Research Council MRC Human Reproductive Sciences Unit, The Queen s Medical Research Institute, Edinburgh, Scotland, United Kingdom
    Mol Endocrinol 24:261-74. 2010
    ..These included fatty acid-specific GPCRs expressed in pancreatic beta-cells and novel neuroendocrine GPCRs regulating reproduction...
  4. pmc Kisspeptin signalling in the hypothalamic arcuate nucleus regulates GnRH pulse generator frequency in the rat
    Xiao Feng Li
    Division of Reproduction and Endocrinology, King s College London, London, United Kingdom
    PLoS ONE 4:e8334. 2009
    ..As the ARC is known to be the site of the gonadotropin-releasing hormone (GnRH) pulse generator we explored whether kisspeptin-GPR54 signalling in the ARC regulates GnRH pulses...
  5. pmc A novel mammalian receptor for the evolutionarily conserved type II GnRH
    R Millar
    Medical Research Council Human Reproductive Sciences Unit, Edinburgh EH3 9ET, Scotland
    Proc Natl Acad Sci U S A 98:9636-41. 2001
    ..Surprisingly, the type II receptor is expressed in the majority of gonadotropes. The presence of two GnRH receptors in gonadotropes, together with the differences in their signaling, suggests different roles in gonadotrope functioning...
  6. pmc Diversity of actions of GnRHs mediated by ligand-induced selective signaling
    Robert P Millar
    MRC Human Reproductive Sciences Unit, The Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
    Front Neuroendocrinol 29:17-35. 2008
    ..This ligand-induced selective-signaling recruits certain pathways while by-passing others and has implications in developing more selective GnRH analogs for highly specific therapeutic intervention...
  7. ncbi request reprint GnRH II and type II GnRH receptors
    Robert P Millar
    MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Chancellor s Building, 49 Little France Crescent, Old Dalkeith Road, Edinburgh EH16 4SB, UK
    Trends Endocrinol Metab 14:35-43. 2003
    ..The conservation of structure over 500 million years and the wide tissue distribution of GnRH II suggest that it has a variety of reproductive and nonreproductive functions and will be a productive area of research...
  8. pmc The chicken type III GnRH receptor homologue is predominantly expressed in the pituitary, and exhibits similar ligand selectivity to the type I receptor
    Nerine T Joseph
    Royal Dick School of Veterinary Studies, The Roslin Institute, University of Edinburgh, Roslin, Midlothian, Edinburgh, UK
    J Endocrinol 202:179-90. 2009
    ....
  9. pmc Transcript and protein profiling identifies signaling, growth arrest, apoptosis, and NF-κB survival signatures following GNRH receptor activation
    Colette Meyer
    Breakthrough Breast Cancer Research Unit and Division of Pathology, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road South, Edinburgh, UK
    Endocr Relat Cancer 20:123-36. 2013
    ....
  10. doi request reprint A crucial role for Galphaq/11, but not Galphai/o or Galphas, in gonadotropin-releasing hormone receptor-mediated cell growth inhibition
    Colin D White
    The Medical Research Council Human Reproductive Sciences Unit, The Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom
    Mol Endocrinol 22:2520-30. 2008
    ....
  11. ncbi request reprint Inhibition of human type i gonadotropin-releasing hormone receptor (GnRHR) function by expression of a human type II GnRHR gene fragment
    Adam J Pawson
    Human Reproductive Sciences Unit, Medical Research Council, The University of Edinburgh Chancellor s Building, 49 Little France Crescent, Edinburgh EH16 4SB, Scotland, United Kingdom
    Endocrinology 146:2639-49. 2005
    ..We suggest that the GnRHR-II-reliquum plays a modulatory role in GnRHR-I expression...
  12. doi request reprint Retention and silencing of prepro-GnRH-II and type II GnRH receptor genes in mammals
    Alan J Stewart
    MRC Human Reproductive Sciences Unit, Queen s Medical Research Institute, Edinburgh, UK
    Neuroendocrinology 90:416-32. 2009
    ..The genetic information will be useful for understanding the physiological role of the GnRH-II system and establishing animal models for functional studies...
  13. doi request reprint Changes to gonadotropin-releasing hormone (GnRH) receptor extracellular loops differentially affect GnRH analog binding and activation: evidence for distinct ligand-stabilized receptor conformations
    Kevin D G Pfleger
    Medical Research Council Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen s Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom
    Endocrinology 149:3118-29. 2008
    ....
  14. ncbi request reprint Sheep exhibit novel variations in the organization of the mammalian type II gonadotropin-releasing hormone receptor gene
    Paula M Gault
    Medical Research Council Human Reproductive Sciences Unit, University of Edinburgh Academic Centre, Edinburgh EH16 4SB, United Kingdom
    Endocrinology 145:2362-74. 2004
    ..Testis and pituitary sections were negative with exon 1 riboprobes and exon 1 or 2-3 oligonucleotide probes in in situ hybridization. A hepta-helical type II GnRH receptor is therefore not expressed from this sheep gene...
  15. ncbi request reprint GnRH-mediated DAN production regulates the transcription of the GnRH receptor in gonadotrope cells
    Rakel Lopez de Maturana
    MRC Human Reproductive Sciences Unit, Centre for Human Reproductive Biology, Edinburgh, EH16 4SB, UK
    Neuromolecular Med 9:230-48. 2007
    ....
  16. ncbi request reprint Bovine and ovine gonadotropin-releasing hormone (GnRH)-II ligand precursors and type II GnRH receptor genes are functionally inactivated
    Kevin Morgan
    Medical Research Council, Human Reproductive Sciences Unit, The Queens Medical Research Institute, Little France Crescent, Old Dalkeith Road, Edinburgh, Scotland EH16 4TJ, United Kingdom
    Endocrinology 147:5041-51. 2006
    ....
  17. pmc Prokineticin 1 modulates IL-8 expression via the calcineurin/NFAT signaling pathway
    David Maldonado-Pérez
    Human Reproductive Sciences Unit, Medical Research Council, Edinburgh EH16 4TJ, UK
    Biochim Biophys Acta 1793:1315-24. 2009
    ..Our findings show that in endometrial cells PROK1 can activate the calcineurin/NFAT pathway to induce IL-8 expression and that this is negatively modulated by the induction of expression of RCAN1-4...
  18. ncbi request reprint Mutations remote from the human gonadotropin-releasing hormone (GnRH) receptor-binding sites specifically increase binding affinity for GnRH II but not GnRH I: evidence for ligand-selective, receptor-active conformations
    Zhi Liang Lu
    Medical Research Council Human Reproductive Sciences Unit, Centre for Reproductive Biology, Edinburgh, Scotland, UK
    J Biol Chem 280:29796-803. 2005
    ..The findings suggest that GnRH I and II binding may selectively stabilize different receptor-active conformations and therefore different ligand-induced selective signaling described previously for these ligands...
  19. pmc GnRH receptor activation competes at a low level with growth signaling in stably transfected human breast cell lines
    Kevin Morgan
    Medical Research Council Human Reproductive Sciences Unit, The Queen s Medical Research Institute, Little France Crescent, Old Dalkeith Road, Edinburgh EH16 4TJ, UK
    BMC Cancer 11:476. 2011
    ..GnRH receptor (GnRH-R) activation also directly inhibits the growth of certain cells. The applicability of GnRH anti-proliferation to breast cancer was therefore analyzed...
  20. pmc Reciprocal cross talk between gonadotropin-releasing hormone (GnRH) and prostaglandin receptors regulates GnRH receptor expression and differential gonadotropin secretion
    Zvi Naor
    Medical Research Council MRC, Huamn Reproduction Sciences, Centre for Reproductive Biology, The Queen s Medical Research Institute, Edinburgh, United Kingdom
    Mol Endocrinol 21:524-37. 2007
    ....
  21. pmc Identification of androgen receptor phosphorylation in the primate ovary in vivo
    Iain J McEwan
    MRC Human Reproductive Sciences Unit, Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, UK
    Reproduction 140:93-104. 2010
    ..These results demonstrate that phosphorylation of the AR occurs, at a subset of serine residues, in a reproductive target tissue in vivo, which appears refractory to hormonal manipulations...
  22. doi request reprint Identification of Tyr(290(6.58)) of the human gonadotropin-releasing hormone (GnRH) receptor as a contact residue for both GnRH I and GnRH II: importance for high-affinity binding and receptor activation
    Marla Coetsee
    MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, United Kingdom
    Biochemistry 47:10305-13. 2008
    ..Tyr (290(6.58)) mutations, except for Y290F, caused larger decreases in GnRH potency than affinity, indicating that an aromatic ring is important for the agonist-induced receptor conformational switch...
  23. pmc Prokineticin 1 signaling and gene regulation in early human pregnancy
    Jemma Evans
    Medical Research Council Human Reproductive Sciences Unit, The Queen s Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom
    Endocrinology 149:2877-87. 2008
    ..These data demonstrate that PROK1 and PROKR1 expression is elevated in human decidua during early pregnancy and that PROK1-PROKR1 interaction regulates expression of a host of implantation-related genes...
  24. pmc Gonadotropin-releasing hormone analog structural determinants of selectivity for inhibition of cell growth: support for the concept of ligand-induced selective signaling
    Rakel Lopez de Maturana
    Ardana Bioscience, Edinburgh, UK
    Mol Endocrinol 22:1711-22. 2008
    ..These findings provide the basis for the development of selective GnRH analog cancer therapeutics that directly target tumor cells or inhibit pituitary gonadotropins or do both...
  25. ncbi request reprint Mammalian type I gonadotropin-releasing hormone receptors undergo slow, constitutive, agonist-independent internalization
    Adam J Pawson
    Medical Research Council Human Reproductive Sciences Unit, The Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom
    Endocrinology 149:1415-22. 2008
    ....
  26. ncbi request reprint Structural determinants for ligand-receptor conformational selection in a peptide G protein-coupled receptor
    Zhi Liang Lu
    Medical Research Council Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, United Kingdom
    J Biol Chem 282:17921-9. 2007
    ..These results reveal GnRH ligand and receptor structural elements for conformational selection, and support co-evolution of GnRH ligand and receptor conformations...
  27. pmc Congenital hypogonadotropic hypogonadism due to GnRH receptor mutations in three brothers reveal sites affecting conformation and coupling
    Javier A Tello
    Centre for Integrative Physiology, School of Biomedical Sciences, University of Edinburgh, Edinburgh, United Kingdom
    PLoS ONE 7:e38456. 2012
    ..Together these molecular deficiencies of the two novel GNRHR1 mutations lead to the CHH phenotype when present as a compound heterozygote...
  28. ncbi request reprint Type II gonadotrophin-releasing hormone (GnRH-II) in reproductive biology
    Adam J Pawson
    Human Reproductive Sciences Unit, Medical Research Council, Edinburgh EH16 4SB, UK
    Reproduction 126:271-8. 2003
    ..Surprises concerning the complexities of GnRH ligand and receptor function in reproductive endocrinology should continue to emerge in the future...
  29. ncbi request reprint A transcriptionally active human type II gonadotropin-releasing hormone receptor gene homolog overlaps two genes in the antisense orientation on chromosome 1q.12
    Kevin Morgan
    Medical Research Council Human Reproductive Sciences Unit, University of Edinburgh Academic Centre, Edinburgh EH16 4SB, United Kingdom
    Endocrinology 144:423-36. 2003
    ..A stem-loop motif resembling a selenocysteine insertion sequence and a potential alternative translation initiation site might enable expression of further proteins involved in interactions within the GnRH system...
  30. doi request reprint Reproductive physiology of a humanized GnRH receptor mouse model: application in evaluation of human-specific analogs
    Javier A Tello
    Centre for Integrative Physiology, School of Biomedical Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Am J Physiol Endocrinol Metab 305:E67-77. 2013
    ..This novel model provides the opportunity to study the human receptor in vivo and for screening the activity of human-specific GnRH analogs...
  31. ncbi request reprint Identification of a novel ligand binding residue Arg38(1.35) in the human gonadotropin-releasing hormone receptor
    Alan J Stewart
    MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom
    Mol Pharmacol 73:75-81. 2008
    ..The mutagenesis results support the prediction of molecular modeling that Arg(38(1.35)) interacts with the C-terminal glycinamide and probably forms hydrogen bonds with the backbone carbonyl of Pro(9) and Gly(10)-NH(2)...
  32. doi request reprint Antiproliferative effects of GnRH agonists: prospects and problems for cancer therapy
    Colin D White
    Medical Research Council Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen s Medical Research Institute, Edinburgh, UK
    Neuroendocrinology 88:67-79. 2008
    ....
  33. pmc Proline-rich tyrosine kinase 2 mediates gonadotropin-releasing hormone signaling to a specific extracellularly regulated kinase-sensitive transcriptional locus in the luteinizing hormone beta-subunit gene
    Stuart Maudsley
    Medical Research Council Human Reproductive Sciences Unit, The Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, United Kingdom
    Mol Endocrinol 21:1216-33. 2007
    ....
  34. doi request reprint Gonadotropin-releasing hormone receptor levels and cell context affect tumor cell responses to agonist in vitro and in vivo
    Kevin Morgan
    Medical Research Council Human Reproductive Sciences Unit, Edinburgh Cancer Research Centre, Edinburgh, United Kingdom
    Cancer Res 68:6331-40. 2008
    ..Further studies should exploit the growth-inhibitory potential of GnRH receptor activation in abnormal cells in diseased human tissues...
  35. doi request reprint Kisspeptin antagonists: unraveling the role of kisspeptin in reproductive physiology
    Robert P Millar
    Medical Research Council Human Reproductive Sciences Unit, Edinburgh, UK
    Brain Res 1364:81-9. 2010
    ..These studies establish that kisspeptin antagonists are powerful investigative tools and set the scene for more extensive physiological and pathophysiological studies as well as therapeutic intervention...
  36. doi request reprint Exploring the pathophysiology of hypogonadism in men with type 2 diabetes: kisspeptin-10 stimulates serum testosterone and LH secretion in men with type 2 diabetes and mild biochemical hypogonadism
    Jyothis T George
    MRC Centre for Reproductive Health, The Queen s Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK
    Clin Endocrinol (Oxf) 79:100-4. 2013
    ..Low serum testosterone is commonly observed in men with type 2 diabetes (T2DM), but the neuroendocrine pathophysiology remains to be elucidated...
  37. ncbi request reprint Gonadotropin-releasing hormone (GnRH) antagonists promote proapoptotic signaling in peripheral reproductive tumor cells by activating a Galphai-coupling state of the type I GnRH receptor
    Stuart Maudsley
    Medical Research Council Human Reproductive Sciences Unit, Edinburgh, United Kingdom
    Cancer Res 64:7533-44. 2004
    ..Therefore the ability of GnRH receptor antagonists to exert an antiproliferative effect on reproductive tumors may be dependent on ligand-selective activation of the Galpha(i)-coupled form of the type I GnRH receptor...
  38. doi request reprint Elevated GnRH receptor expression plus GnRH agonist treatment inhibits the growth of a subset of papillomavirus 18-immortalized human prostate cells
    Kevin Morgan
    Medical Research Council Human Reproductive Sciences Unit, The Queen s Medical Research Institute, Little France Crescent, Edinburgh, UK
    Prostate 71:915-28. 2011
    ..Human metastatic prostate cancer cell growth can be inhibited by GnRH analogs but effects on virus-immortalized prostate cells have not been investigated...
  39. ncbi request reprint Two mutations in extracellular loop 2 of the human GnRH receptor convert an antagonist to an agonist
    Thomas R Ott
    Medical Research Council Human Reproductive Sciences Unit, Edinburgh EH3 9ET, United Kingdom
    Mol Endocrinol 16:1079-88. 2002
    ..32(205)) to stabilize the receptor in the active conformation. This discovery highlights the importance of EL-2 in ligand binding and receptor activation in G protein-coupled receptors...
  40. ncbi request reprint Nuclear stabilization of beta-catenin and inactivation of glycogen synthase kinase-3beta by gonadotropin-releasing hormone: targeting Wnt signaling in the pituitary gonadotrope
    Samantha Gardner
    Medical Research Council Human Reproductive Sciences Unit, The Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, United Kingdom
    Mol Endocrinol 21:3028-38. 2007
    ..Our findings extend the number of GPCRs that can target beta-catenin signaling through diverse pathways. Furthermore, this is the first demonstration of the targeting of Wnt/beta-catenin signaling by a peptide hormone GPCR...
  41. ncbi request reprint Conformational constraint of mammalian, chicken, and salmon GnRHs, but not GnRH II, enhances binding at mammalian and nonmammalian receptors: evidence for preconfiguration of GnRH II
    Kevin D G Pfleger
    Medical Research Council Human Reproductive Sciences Unit, Edinburgh, EH16 4SB, United Kingdom
    Mol Endocrinol 16:2155-62. 2002
    ..We suggest that this ligand is preconfigured through intramolecular interactions, which accounts for its high binding affinity and total conservation of primary structure over 500 million years of evolution...
  42. pmc Discovery of potent kisspeptin antagonists delineate physiological mechanisms of gonadotropin regulation
    Antonia K Roseweir
    Medical Research Council Human Reproductive Sciences Unit, The Queens Medical Research Institute, Edinburgh EH16 4TJ, UK
    J Neurosci 29:3920-9. 2009
    ....
  43. ncbi request reprint Evolution of GnRH ligand precursors and GnRH receptors in protochordate and vertebrate species
    Kevin Morgan
    MRC Human Reproductive Sciences Unit, Old Dalkeith Road, Edinburgh EH16 4SB, UK
    Gen Comp Endocrinol 139:191-7. 2004
    ..For instance, recent data show that even species as closely related as humans and chimpanzees exhibit important organisational changes in the genes comprising the GnRH system...
  44. doi request reprint Kisspeptin-10 inhibits angiogenesis in human placental vessels ex vivo and endothelial cells in vitro
    Thayalini Ramaesh
    Jennifer Brown Research Laboratory, Centre for Cardiovascular Science, Queen s Medical Research Institute, Edinburgh, UK
    Endocrinology 151:5927-34. 2010
    ..In conclusion, KP-10 has antiangiogenic effects and, given its high expression in the placenta, may contribute to the regulation of angiogenesis in this tissue...
  45. doi request reprint Differential expression and functional characterization of luteinizing hormone receptor splice variants in human luteal cells: implications for luteolysis
    Rachel E Dickinson
    Department of Reproductive and DevelopmentalSciences, Division of Obstetrics and Gynaecology, Centre for Reproductive Biology, The Queen s Medical Research Institute, Edinburgh, United Kingdom
    Endocrinology 150:2873-81. 2009
    ..Overall, these results imply expression of LHR splice variants is regulated in the human CL. Furthermore, during functional luteolysis a truncated variant could modulate the cell surface expression and activity of full-length LHR...
  46. ncbi request reprint Gonadotropin-releasing hormone functionally antagonizes testosterone activation of the human androgen receptor in prostate cells through focal adhesion complexes involving Hic-5
    Stuart Maudsley
    Medical Research Council Human Reproductive Sciences Unit, The Queen s Medical Research Institute, and Ardana Bioscience, Edinburgh, UK
    Neuroendocrinology 84:285-300. 2006
    ..This antagonism of testosterone action by GnRH may underlie in part the capacity of GnRH receptor activation to inhibit prostate tumor growth...
  47. pmc GPR54-dependent stimulation of luteinizing hormone secretion by neurokinin B in prepubertal rats
    Pasha Grachev
    Division of Women s Health, School of Medicine, King s College London, London, United Kingdom
    PLoS ONE 7:e44344. 2012
    ..These data demonstrate that the stimulatory effect of NKB on LH secretion in intact female rats is dependent upon kisspeptin/GPR54 signaling, but not on Dyn signaling...
  48. doi request reprint Hypothesis: kisspeptin mediates male hypogonadism in obesity and type 2 diabetes
    Jyothis T George
    Medical Research Council, Human Reproductive Sciences Unit, University of Edinburgh, Centre for Reproductive Biology, The Queen s Medical Research Institute, Edinburgh, UK
    Neuroendocrinology 91:302-7. 2010
    ....
  49. ncbi request reprint Bifunctional gonadotropin-releasing hormone antagonist-progesterone analogs with increased efficacy and duration of action
    Karen E Ratcliffe
    Medical Research Council, Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen s Medical Research Institute, Edinburgh EH16 4TJ, Scotland, United Kingdom
    Endocrinology 147:571-9. 2006
    ..These new GnRH antagonists show promise as therapeutic agents for hormone-dependent diseases and as contraceptives...
  50. pmc Potential roles of the prokineticins in reproduction
    David Maldonado-Pérez
    MRC Human Reproductive Sciences Unit, The Queen s Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
    Trends Endocrinol Metab 18:66-72. 2007
    ..Their expression has also been reported in various pathologies of the reproductive tract, and future studies will highlight whether inhibition of prokineticin function in these pathologies would be a useful therapeutic target...
  51. ncbi request reprint Gonadotropin-releasing hormone-induced activation of diacylglycerol kinase-zeta and its association with active c-src
    Lindsay Davidson
    MRC Human Reproductive Sciences Unit, Edinburgh Royal Infirmary, The University of Edinburgh Chancellor s Building, 49 Little France Crescent, Edinburgh EH16 4SB, Scotland, United Kingdom
    J Biol Chem 279:11906-16. 2004
    ..Elevated expression of DGK-zeta resulted in a shortening of the time scale of ERK activation in these cells suggesting a potential role of endogenous DGK-zeta in controlling the induction of LHbeta transcription by ERK1/2...
  52. pmc Interactions Between Neurokinin B and Kisspeptin in Mediating Estrogen Feedback in Healthy Women
    Karolina Skorupskaite
    MRC Centre for Reproductive Health K S, J T G, R A A, The Queen s Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom Endocrine Research Unit J D V, Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905 and Mammal Research Unit and Centre for Neuroendocrinology R P M, University of Pretoria, 0028 Pretoria, South Africa and MRC Receptor Biology Unit, Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, 7925 Observatory, South Africa
    J Clin Endocrinol Metab 101:4628-4636. 2016
    ..Kisspeptin and neurokinin B (NKB) are obligate for normal gonadotropin secretion, but their hierarchy is unexplored in normal women...
  53. doi request reprint Kisspeptin antagonists
    Antonia Kathryn Roseweir
    University of Strathclyde, Glasgow, Scotland, UK
    Adv Exp Med Biol 784:159-86. 2013
    ..To date, four peptide antagonists and one small molecule antagonist have been designed...
  54. ncbi request reprint Phospholipase C-eta enzymes as putative protein kinase C and Ca2+ signalling components in neuronal and neuroendocrine tissues
    Alan J Stewart
    MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen s Medical Research Institute, Edinburgh, UK
    Neuroendocrinology 86:243-8. 2007
    ..PLCeta enzymes therefore represent novel proteins influencing intracellular Ca2+ dynamics and protein kinase C activation in the brain and neuroendocrine systems as putative mediation of GPCR regulation...
  55. ncbi request reprint Cytoskeletal reorganization dependence of signaling by the gonadotropin-releasing hormone receptor
    Lindsay Davidson
    Medical Research Council Human Reproductive Sciences Unit, Edinburgh Royal Infirmary, The University of Edinburgh Chancellor s Building, 49 Little France Crescent, Edinburgh EH16 4SB, Scotland, United Kingdom
    J Biol Chem 279:1980-93. 2004
    ....
  56. ncbi request reprint Amygdala Kisspeptin Neurons: Putative Mediators of Olfactory Control of the Gonadotropic Axis
    Rafael Pineda
    Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh, UK
    Neuroendocrinology . 2016
    ....
  57. doi request reprint A role for kisspeptins in pregnancy: facts and speculations
    Rebecca M Reynolds
    Endocrinology Unit, Centre for Cardiovascular Sciences, Jennifer Brown Research Laboratory, Queen s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
    Reproduction 138:1-7. 2009
    ..Here, we review the literature regarding the role and physiological significance of kisspeptin in pregnancy and highlight some of the key questions that require addressing...
  58. pmc Seminal plasma activates cyclooxygenase-2 and prostaglandin E2 receptor expression and signalling in cervical adenocarcinoma cells
    Kurt J Sales
    MRC Human Reproductive Sciences Unit, Academic Centre, 49 Little France Crescent, Old Dalkeith Road, Edinburgh EH16 4SB, UK
    Mol Hum Reprod 8:1065-70. 2002
    ..05). These data suggest that, in sexually active women, seminal plasma may play a role in modulating neoplastic cell function and cervical tumorigenesis...
  59. ncbi request reprint Identification of Ser153 in ICL2 of the gonadotropin-releasing hormone (GnRH) receptor as a phosphorylation-independent site for inhibition of Gq coupling
    Sharon Shacham
    Department of Biochemistry, George S Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, Israel
    J Biol Chem 280:28981-8. 2005
    ..Because the phosphomimetic ICL2-S153E peptide did not mimic the stimulatory effect of the ICL2 peptide, the inhibitory effect of Ser153 operates through a phosphorylation-independent mechanism...
  60. ncbi request reprint An evolutionarily conserved form of gonadotropin-releasing hormone coordinates energy and reproductive behavior
    Jennifer L Temple
    Program in Neuroscience, University of Virginia Medical School, Charlottesville, Virginia 22908, USA
    Endocrinology 144:13-9. 2003
    ..Our results lead us to hypothesize that the role of the evolutionarily conserved GnRH-II peptide is to coordinate reproductive behavior as appropriate to the organism's energetic condition...
  61. ncbi request reprint Differential brain distribution of gonadotropin-releasing hormone receptors in the goldfish
    Richard E Peter
    Department of Biological Sciences, University of Alberta, Alta, T6G 2E9 Edmonton, Canada
    Gen Comp Endocrinol 132:399-408. 2003
    ....
  62. ncbi request reprint Multiple determinants for rapid agonist-induced internalization of a nonmammalian gonadotropin-releasing hormone receptor: a putative palmitoylation site and threonine doublet within the carboxyl-terminal tail Are critical
    Adam J Pawson
    Human Reproductive Sciences Unit, Medical Research Council, Edinburgh, United Kingdom EH16 4SB
    Endocrinology 144:3860-71. 2003
    ..Furthermore, cGnRH-Rs appeared to be mobilized to the beta-arrestin- and clathrin-coated, vesicle-mediated endocytic pathway upon beta-arrestin overexpression...
  63. ncbi request reprint Pro7.33(303) of the human GnRH receptor regulates selective binding of mammalian GnRH
    Bernhard J Fromme
    UCT MRC Research Group for Receptor Biology, Institute for Infectious Diseases and Molecular Medicine, Division of Medical Biochemistry, University of Cape Town Faculty of Health Sciences, Observatory, Cape Town, 7925, South Africa
    Mol Cell Endocrinol 219:47-59. 2004
    ..33(303) of the human GnRH receptor is required for selective high affinity binding of mammalian GnRH and supports the hypothesis that Pro7.33(303) stabilises a loop conformation that is necessary for selective ligand binding...
  64. ncbi request reprint Serine residues 338 and 339 in the carboxyl-terminal tail of the type II gonadotropin-releasing hormone receptor are critical for beta-arrestin-independent internalization
    Katharina Ronacher
    Medical Research Council Research Group for Receptor Biology, Division of Medical Biochemistry, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, South Africa
    Endocrinology 145:4480-8. 2004
    ..However, neither of these residues, nor the carboxyl-terminal tail, is required for beta-arrestin-dependent internalization...
  65. ncbi request reprint Outside-in and inside-out signaling: the new concept that selectivity of ligand binding at the gonadotropin-releasing hormone receptor is modulated by the intracellular environment
    Robert P Millar
    Endocrinology 145:3590-3. 2004
  66. ncbi request reprint Evolution of constrained gonadotropin-releasing hormone ligand conformation and receptor selectivity
    Perdita E Barran
    School of Chemistry, The University of Edinburgh, Edinburgh EH9 3JJ, United Kingdom
    J Biol Chem 280:38569-75. 2005
    ....
  67. ncbi request reprint Expression of gonadotropin-releasing hormone II (GnRH-II) receptor in human endometrial and ovarian cancer cells and effects of GnRH-II on tumor cell proliferation
    Carsten Gründker
    Department of Gynecology and Obstetrics, Georg August University, D 37070 Gottingen, Germany
    J Clin Endocrinol Metab 87:1427-30. 2002
    ..001). In the GnRH-II receptor positive but GnRH-I receptor negative ovarian cancer cell line SK-OV-3 native GnRH-II but not GnRH-I agonist Triptorelin had antiproliferative effects...
  68. ncbi request reprint Hypothalamic GnRH-I and its precursor during photorefractoriness onset in free-living male Dark-eyed Juncos (Junco hyemalis) of different year classes
    Simone L Meddle
    Laboratory of Neuroendocrinology, Centre for Integrative Physiology, School of Veterinary Biomedical Sciences, Royal Dick School of Veterinary Medicine, Summerhall, Edinburgh EH9 1QH, UK
    Gen Comp Endocrinol 145:148-56. 2006
    ..Instead, the regulation of GnRH-I secretion by non-photoperiodic factors may determine photorefractoriness onset...
  69. ncbi request reprint Conserved amino acid residues that are important for ligand binding in the type I gonadotropin-releasing hormone (GnRH) receptor are required for high potency of GnRH II at the type II GnRH receptor
    Sipho Mamputha
    Medical Research Council University of Cape Town Research Group for Receptor Biology, Institute for Infectious Diseases and Molecular Medicine and Division of Medical Biochemistry, Cape Town, South Africa
    Mol Endocrinol 21:281-92. 2007
    ..This suggests that Lys3.32(120) recognizes agonists, but not antagonists, as in the type I receptor. These data indicate that roles of conserved residues are similar, but not identical, in the type I and II GnRH receptors...
  70. ncbi request reprint Molecular genetic analysis of normosmic hypogonadotropic hypogonadism in a Turkish population: identification and detailed functional characterization of a novel mutation in the gonadotropin-releasing hormone receptor gene
    A Kemal Topaloglu
    Division of Paediatric Endocrinology and Metabolism, Cukurova University, Faculty of Medicine, Adana, Turkey
    Neuroendocrinology 84:301-8. 2006
    ..Currently known mutations account for less than 15% of cases with normosmic hypogonadotropic hypogonadism (nIHH). The objective of the study was to identify novel hereditary associations in the pathogenesis of nIHH...
  71. pmc Cyclooxygenase-1 is up-regulated in cervical carcinomas: autocrine/paracrine regulation of cyclooxygenase-2, prostaglandin e receptors, and angiogenic factors by cyclooxygenase-1
    Kurt J Sales
    Department of Medical Biochemistry, University of Cape Town Medical School, Cape Town 7925, South Africa
    Cancer Res 62:424-32. 2002
    ..It is likely that similar mechanisms may act in vivo to modulate tumorigenesis of cervical carcinomas...
  72. ncbi request reprint Photoperiod-independent hypothalamic regulation of luteinizing hormone secretion in a free-living Sonoran desert bird, the Rufous-winged Sparrow (Aimophila carpalis)
    Thomas W Small
    School of Life Sciences, Arizona State University, Tempe, Ariz 85287 4501, USA
    Brain Behav Evol 71:127-42. 2008
    ..These data also suggest that GnIH could inhibit GnRH neuronal activity prior to the monsoon season...
  73. ncbi request reprint Localization of the three GnRH types and GnRH receptors in the brain of a cichlid fish: Insights into their neuroendocrine and neuromodulator functions
    Tomoko Soga
    Department of Physiology, Nippon Medical School, Sendagi, Tokyo 113 8602, Japan
    J Comp Neurol 487:28-41. 2005
    ..Further, evidence of close proximity of GnRH-R-containing cells and neuronal processes of multiple GnRH types suggests complex cross-talk between several GnRH ligands and GnRH-Rs...
  74. ncbi request reprint Gonadotropin-releasing hormone II stimulates female sexual behavior in marmoset monkeys
    Deborah K Barnett
    National Primate Research Center, University of Wisconsin, Madison, Wisconsin 53715, USA
    Endocrinology 147:615-23. 2006
    ..These findings implicate a role for GnRH II and the cognate GnRH type II receptor in stimulating female marmoset sexual behavior...
  75. ncbi request reprint Activation of mitogen-activated protein kinase (MAPK) by GnRH is cell-context dependent
    Masha Dobkin-Bekman
    Department of Biochemistry, The George S Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, Israel
    Mol Cell Endocrinol 252:184-90. 2006
    ..The above pathways mediate GnRH-induced gonadotropin release and synthesis. Here we summarise the diverse mechanisms utilized by GnRH to activate the MAPK members and show that they depend on "cell-context"...
  76. ncbi request reprint Auditory stimulation of reproductive function in male Rufous-winged Sparrows, Aimophila carpalis
    Thomas W Small
    School of Life Sciences, Arizona State University, Tempe, AZ 85287 4501, USA
    Horm Behav 53:28-39. 2008
    ..These data indicate that long-term exposure to auditory stimuli, such as song, can influence the reproductive system of male songbirds and different types of auditory stimuli can have differential effects on reproductive function...