title: Stress-dependent and gender-specific neuroregulatory roles of the apelin receptor in the hypothalamic-pituitary-adrenal axis response to acute stress.
abstract: The neuropeptide apelin is expressed in hypothalamic paraventricular and supraoptic nuclei and mediates its effects via activation of the apelin receptor (APJ). Evidence suggests a role for apelin and APJ in mediating the neuroendocrine response to stress. To understand the physiological role of APJ in regulation of the hypothalamic-pituitary-adrenal (HPA) axis, we measured ACTH and corticosterone (CORT) plasma levels in male and female mice lacking APJ (APJ knockout, APJ KO) and in wild-type controls, in response to a variety of acute stressors. Exposure to mild restraint, systemic injection of lipopolysaccharide (LPS), insulin-induced hypoglycaemia and forced swim (FS) stressors, elevated plasma ACTH and CORT levels in wild-type mice. Acute mild restraint significantly increased plasma ACTH and CORT to a similar level in APJ KO mice as in wild-type mice. However, an intact APJ was required for a conventional ACTH, but not CORT, response to LPS administration in male mice and to insulin-induced hypoglycaemia in male and female mice. In contrast, APJ KO mice displayed an impaired CORT response to acute FS stress, regardless of gender. These data indicate that APJ has a role in regulation of the HPA axis response to some acute stressors and has a gender-specific function in peripheral immune activation of the HPA axis.
authors.affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (LINE), School of Clinical Sciences, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK.
authors.forename: M J F
authors.initials: MJ
authors.lastname: Newson
authors.forename: G R
authors.initials: GR
authors.lastname: Pope
authors.forename: E M
authors.initials: EM
authors.lastname: Roberts
authors.forename: S J
authors.initials: SJ
authors.lastname: Lolait
authors.forename: A-M
authors.initials: AM
authors.lastname: O'Carroll
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000818:Animals; D000075244:Apelin Receptors; D002940:Circadian Rhythm; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D050505:Mutant Proteins / Q000378:metabolism; D055099:Neuroendocrine Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010913:Pituitary-Adrenal System / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D012727:Sex Characteristics; D013312:Stress, Physiological; D013315:Stress, Psychological / Q000097:blood / Q000276:immunology / Q000378:metabolism*
chemical_list: D000075244:Apelin Receptors; C491285:Aplnr protein, mouse; D050505:Mutant Proteins; D043562:Receptors, G-Protein-Coupled; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone