title: Neuroendocrine responses to stress in mice: hyporesponsiveness in pregnancy and parturition.
abstract: Hypothalamo-pituitary-adrenal axis secretory responses to stress were compared in female virgin, late pregnant, parturient, and lactating mice. The basal plasma ACTH concentration was not different in pregnancy or lactation compared with virgins, but corticosterone concentration and corticosteroid-binding globulin capacity were greatly elevated in late pregnancy. Secretory responses to novel environment were attenuated in pregnant, but not lactating, mice compared with virgin females, whereas ACTH responses to forced swimming were attenuated in both groups. The expression of immediate early gene (nur77) mRNA increased in paraventricular nucleus neurons after stress exposure in virgin and lactating, but not pregnant, mice. During parturition, the basal ACTH concentration was similar to virgin and pregnant controls and did not increase with stress. Oxytocin secretion in response to either novel environment or forced swimming was unchanged in any reproductive group, whereas vasopressin secretion was decreased by both stressors, but only in virgins. Pretreatment with oxytocin receptor antagonist centrally had no effect on ACTH responses to stress in either virgin or pregnant mice. Pretreatment with an opioid receptor antagonist increased ACTH responses to stress in virgin mice, indicating opioid inhibition, but had no effect in pregnancy. Thus, in mice hypothalamo-pituitary-adrenal hyporesponsiveness in late pregnancy is a consequence of reduced responsiveness of paraventricular neurons, but inhibition by opioids or intracerebral oxytocin does not appear to be involved.
authors.affiliation: Division of Biomedical Sciences, School of Biomedical and Clinical Laboratory Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh, United Kingdom EH8 9XD. alison.j.douglas@ed.ac.uk.
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Douglas
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Brunton
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Bosch
authors.forename: John A
authors.initials: JA
authors.lastname: Russell
authors.forename: Inga D
authors.initials: ID
authors.lastname: Neumann
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000818:Animals; D021461:Animals, Outbred Strains; D002352:Carrier Proteins / Q000097:blood; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000502:physiology*; D007276:Injections, Intraventricular; D007774:Lactation / Q000502:physiology; D051379:Mice; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018847:Opioid Peptides / Q000502:physiology; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology; D036801:Parturition / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000502:physiology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D013312:Stress, Physiological / Q000503:physiopathology*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018847:Opioid Peptides; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; C082249:F 327; D010121:Oxytocin; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone