title: 17Beta-oestradiol modulates glucocorticoid, neural and behavioural adaptations to repeated restraint stress in female rats.
abstract: Sex steroids have a role in modulating responses that extends beyond reproduction. The current study investigated the influence of the sex steroid 17beta-oestradiol on hypothalamic-pituitary-adrenal (HPA) and behavioural responses to acute or repeated restraint stress. Ovariectomized rats treated with 17beta-oestradiol or peanut oil via a subcutaneous silastic capsule were subjected to daily handling (non stressed), acute (single, 1 h) or daily (10 days, 1 h/day) restraint stress. Blood collected at the end of stress revealed that 17beta-oestradiol treatment augmented the corticosterone response to acute restraint. After daily exposure to restraint, the corticosterone response was noticeably diminished in untreated females but 17beta-oestradiol-treated rats still showed an exaggerated response compared to castrated, untreated females. Brain tissue collected 3 h after the end of restraint was probed using isotopic in situ hybridization for corticotropin-releasing factor (CRF) and vasopressin gene expression in the paraventricular nucleus (PVN) of the hypothalamus. 17beta-oestradiol treatment at the higher dose (120 microg/ml) decreased basal CRF mRNA. Stress caused an increase in CRF mRNA expression in 17beta-oestradiol-treated rats but not in the vehicle group. Repeated restraint stress caused an increase in PVN parvocellular vasopressin gene expression, which was more pronounced in 17beta-oestradiol-replaced rats. Animals were exposed to the elevated plus maze for 5 min as a test for anxiety. Non-stressed control rats with or without 17beta-oestradiol replacement spent the same percentage amount of time exploring the open arms of the maze. Previous exposure to acute restraint stress caused a marked reduction in the time spent exploring the open arms, indicating an increase in anxiety levels in these rats; this effect was observed in both vehicle and 17beta-oestradiol-treated rats. After repeated restraint stress, 17beta-oestradiol-replaced rats spent as much time exploring the open arms of the maze as controls, indicating adaptation. By contrast, nonreplaced rats were still showing a significant reduction in open arm exploration after repeated restraint. The present study presents novel data showing that the HPA axis remains reactive to repeated stress in 17beta-oestradiol-treated ovariectomized rats, but stress-induced anxiety behaviour is reduced.
authors.affiliation: Department of Anatomy, University of Cambridge, Cambridge, UK.
authors.forename: P
authors.initials: P
authors.lastname: Lunga
authors.forename: J
authors.initials: J
authors.lastname: Herbert
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000223:Adaptation, Psychological / Q000502:physiology; D000818:Animals; D001007:Anxiety / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000097:blood / Q000502:physiology*; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D006185:Habituation, Psychophysiologic / Q000502:physiology*; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D012149:Restraint, Physical / Q000502:physiology; D013312:Stress, Physiological / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D014667:Vasopressins / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D014667:Vasopressins; D004958:Estradiol; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone