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M Newson, Henry Wellcome LINE, University of Bristol, Bristol, United Kingdom
E Roberts, Henry Wellcome LINE, University of Bristol, Bristol, United Kingdom
G Pope, Henry Wellcome LINE, University of Bristol, Bristol, United Kingdom
S Lolait, Henry Wellcome LINE, University of Bristol, Bristol, United Kingdom
A O'Carroll, Henry Wellcome LINE, University of Bristol, Bristol, BS1 3NY, United Kingdom

Correspondence: Anne-Marie O'Carroll, Email: A.M.OCarroll{at}bristol.ac.uk

The apelinergic system has a widespread expression in the 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 corticotropin 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 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 intracerebroventricular (i.c.v.) administration of pGlu-apelin-13 on neuroendocrine function in male mice pre-treated with the CRF receptor antagonist, alpha-helical CRF9-41 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 adrenocorticotropin releasing hormone (ACTH) and corticosterone (CORT), which were significantly reduced by pre-treatment with alpha-helical CRF9-41, indicating the involvement of a CRF-dependent mechanism, while pGlu-apelin-13- mediated increases in both plasma ACTH and CORT were significantly attenuated in V1bR KO animals when compared to 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.

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