title: The effects of apelin on hypothalamic-pituitary-adrenal axis neuroendocrine function are mediated through corticotrophin-releasing factor- and vasopressin-dependent mechanisms.
abstract: The apelinergic system has a widespread expression in the central nervous system (CNS) including the paraventricular nucleus, supraoptic nucleus and median eminence, and isolated cells of the anterior lobe of the pituitary. This pattern of expression in hypothalamic nuclei known to contain corticotrophin-releasing factor (CRF) and vasopressin (AVP) and to co-ordinate endocrine responses to stress has generated interest in a role for apelin in the modulation of stress, perhaps via the regulation of hormone release from the pituitary. In this study, to determine whether apelin has a central role in the regulation of CRF and AVP neurones, we investigated the effect of i.c.v. administration of pGlu-apelin-13 on neuroendocrine function in male mice pre-treated with the CRF receptor antagonist, alpha-helical CRF(9-41), and in mice-lacking functional AVP V1b receptors (V1bR KO). Administration of pGlu-apelin-13 (1 mg/kg i.c.v.) resulted in significant increases in plasma ACTH and corticosterone (CORT), which were significantly reduced by pre-treatment with alpha-helical CRF(9-41), indicating the involvement of a CRF-dependent mechanism. Additionally, pGlu-apelin-13-mediated increases in both plasma ACTH and CORT were significantly attenuated in V1bR KO animals when compared with wild-type controls, indicating a role for the vasopressinergic system in the regulation of the effects of apelin on neuroendocrine function. Together, these data confirm that the in vivo effects of apelin on hypothalamic-pituitary-adrenal neuroendocrine function appear to be mediated through both CRF- and AVP-dependent mechanisms.
authors.affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, UK.
authors.forename: Michael J F
authors.initials: MJ
authors.lastname: Newson
authors.forename: Emma M
authors.initials: EM
authors.lastname: Roberts
authors.forename: George R
authors.initials: GR
authors.lastname: Pope
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lolait
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: O'Carroll
mesh_terms: D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000097:blood / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D006727:Hormone Antagonists / Q000494:pharmacology; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009490:Neurosecretory Systems / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D017483:Receptors, Vasopressin / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014667:Vasopressins / Q000378:metabolism / Q000502:physiology*
chemical_list: D006727:Hormone Antagonists; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; D017483:Receptors, Vasopressin; C495199:apelin-13 peptide; D014667:Vasopressins; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41); D006854:Hydrocortisone