BACKGROUND AND PURPOSE: The functional characterization of secreted peptides can provide the basis for the development of novel therapeutic agents. Augurin is a recently identified secreted peptide of unknown function expressed in multiple endocrine tissues, and in regions of the brain including the hypothalamus. We therefore investigated the effect of hypothalamic injection of augurin on the hypothalamo-pituitary-adrenal (HPA) axis in male Wistar rats. EXPERIMENTAL APPROACH: Augurin was given as a single injection into the third cerebral ventricle (i.c.v.) or into the paraventricular nucleus (iPVN) of the hypothalamus. Circulating hormone levels were then measured by radioimmunoassay. The effect of augurin on the release of hypothalamic neuropeptides was investigated ex vivo using hypothalamic explants. The acute effects of iPVN augurin on behaviour were also assessed. KEY RESULTS: i.c.v. injection of augurin significantly increased plasma ACTH and corticosterone, compared with vehicle-injected controls, but had no effect on other hypothalamo-pituitary axes hormones. Microinjection of lower doses of augurin into the PVN caused a similar increase in plasma ACTH and corticosterone, without significant alteration in behavioural patterns. Incubation of hypothalamic explants with increasing doses of augurin significantly elevated corticotrophin-releasing factor (CRF) and arginine vasopressin release. In vivo, peripheral injection of a CRF(1/2) receptor antagonist prevented the rise in ACTH and corticosterone caused by i.c.v. augurin injection. CONCLUSIONS AND IMPLICATIONS: These data suggest that augurin stimulates the release of ACTH via the release of hypothalamic CRF. Pharmacological manipulation of the augurin system may therefore be a novel target for regulation of the HPA axis.
BACKGROUND AND PURPOSE: The functional characterization of secreted peptides can provide the basis for the development of novel therapeutic agents. Augurin is a recently identified secreted peptide of unknown function expressed in multiple endocrine tissues, and in regions of the brain including the hypothalamus. We therefore investigated the effect of hypothalamic injection of augurin on the hypothalamo-pituitary-adrenal (HPA) axis in male Wistar rats. EXPERIMENTAL APPROACH: Augurin was given as a single injection into the third cerebral ventricle (i.c.v.) or into the paraventricular nucleus (iPVN) of the hypothalamus. Circulating hormone levels were then measured by radioimmunoassay. The effect of augurin on the release of hypothalamic neuropeptides was investigated ex vivo using hypothalamic explants. The acute effects of iPVN augurin on behaviour were also assessed. KEY RESULTS: i.c.v. injection of augurin significantly increased plasma ACTH and corticosterone, compared with vehicle-injected controls, but had no effect on other hypothalamo-pituitary axes hormones. Microinjection of lower doses of augurin into the PVN caused a similar increase in plasma ACTH and corticosterone, without significant alteration in behavioural patterns. Incubation of hypothalamic explants with increasing doses of augurin significantly elevated corticotrophin-releasing factor (CRF) and arginine vasopressin release. In vivo, peripheral injection of a CRF(1/2) receptor antagonist prevented the rise in ACTH and corticosterone caused by i.c.v. augurin injection. CONCLUSIONS AND IMPLICATIONS: These data suggest that augurin stimulates the release of ACTH via the release of hypothalamic CRF. Pharmacological manipulation of the augurin system may therefore be a novel target for regulation of the HPA axis.
Authors: K E Habib; K P Weld; K C Rice; J Pushkas; M Champoux; S Listwak; E L Webster; A J Atkinson; J Schulkin; C Contoreggi; G P Chrousos; S M McCann; S J Suomi; J D Higley; P W Gold Journal: Proc Natl Acad Sci U S A Date: 2000-05-23 Impact factor: 11.205
Authors: Caroline R Abbott; Adam R Kennedy; Alison M Wren; Michela Rossi; Kevin G Murphy; Leighton J Seal; Jeannie F Todd; Mohammad A Ghatei; Caroline J Small; Stephen R Bloom Journal: Endocrinology Date: 2003-09 Impact factor: 4.736
Authors: Andrew I Su; Tim Wiltshire; Serge Batalov; Hilmar Lapp; Keith A Ching; David Block; Jie Zhang; Richard Soden; Mimi Hayakawa; Gabriel Kreiman; Michael P Cooke; John R Walker; John B Hogenesch Journal: Proc Natl Acad Sci U S A Date: 2004-04-09 Impact factor: 11.205
Authors: Kimberly P Kinzig; David A D'Alessio; James P Herman; Randall R Sakai; Torsten P Vahl; Helmer F Figueiredo; Erin K Murphy; Randy J Seeley; Helmer F Figueredo Journal: J Neurosci Date: 2003-07-16 Impact factor: 6.167
Authors: Waljit S Dhillo; Caroline J Small; Preeti H Jethwa; Sabina H Russell; James V Gardiner; Gavin A Bewick; Asha Seth; Kevin G Murphy; Mohammad A Ghatei; Stephen R Bloom Journal: Endocrinology Date: 2003-04 Impact factor: 4.736
Authors: A M Wren; C J Small; C R Abbott; P H Jethwa; A R Kennedy; K G Murphy; S A Stanley; A N Zollner; M A Ghatei; S R Bloom Journal: Endocrinology Date: 2002-11 Impact factor: 4.736
Authors: Andrew Baird; Raul Coimbra; Xitong Dang; Nicole Lopez; Jisook Lee; Michael Krzyzaniak; Robert Winfield; Bruce Potenza; Brian P Eliceiri Journal: J Leukoc Biol Date: 2012-03-06 Impact factor: 4.962
Authors: Todd W Costantini; Raul Coimbra; Nicole E Lopez; Jeanne G Lee; Bruce Potenza; Alan Smith; Andrew Baird; Brian P Eliceiri Journal: Surg Infect (Larchmt) Date: 2015-10-13 Impact factor: 2.150
Authors: Ana Maria Gonzalez; Sonia Podvin; Shuh-Yow Lin; Miles C Miller; Hannah Botfield; Wendy E Leadbeater; Andrew Roberton; Xitong Dang; Stuart E Knowling; Elena Cardenas-Galindo; John E Donahue; Edward G Stopa; Conrad E Johanson; Raul Coimbra; Brian P Eliceiri; Andrew Baird Journal: Fluids Barriers CNS Date: 2011-01-18
Authors: Sonia Podvin; Ana-Maria Gonzalez; Miles C Miller; Xitong Dang; Hannah Botfield; John E Donahue; Arwa Kurabi; Matthew Boissaud-Cooke; Ryan Rossi; Wendy E Leadbeater; Conrad E Johanson; Raul Coimbra; Edward G Stopa; Brian P Eliceiri; Andrew Baird Journal: PLoS One Date: 2011-09-14 Impact factor: 3.240