title: Effects of prenatal ethanol exposure on hypothalamic-pituitary-adrenal function across the estrous cycle.
abstract: BACKGROUND
  Rats prenatally exposed to ethanol (E) typically show increased hypothalamic-pituitary-adrenal (HPA) responses to stressors in adulthood. Importantly, prenatal ethanol may differentially alter stress responsiveness in male and female offspring, suggesting a role for the gonadal hormones in mediating the effects of ethanol on HPA activity. We investigated the role of ethanol-induced changes in hypothalamic-pituitary-gonadal (HPG) activity in the differential HPA regulation observed in E compared to control females across the estrous cycle.
  
  
  METHODS
  Peripheral hormones and changes in central neuropeptide mRNA levels were measured across the estrous cycle in adult female offspring from E, pair-fed (PF) and ad libitum-fed control (C) dams.
  
  
  RESULTS
  Ethanol females showed normal estrous cyclicity (vaginal smears) but delayed sexual maturation (vaginal opening). Both HPG and HPA activity were differentially altered in E (and in some cases, PF) compared to control females as a function of estrous cycle stage. In relation to HPG activity, E and PF females had higher basal and stress estradiol (E(2)) levels in proestrus compared to other phases of the cycle, and decreased GnRH mRNA levels compared to C females in diestrus. Further, E females had greater variation in LH than PF and C females across the cycle, and in proestrus, only E females showed a significant LH increase following stress. In relation to HPA activity, both basal and stress CORT levels and overall ACTH levels were greater in E than in C females in proestrus. Furthermore, AVP mRNA levels were increased overall in E compared to PF and C females.
  
  
  CONCLUSIONS
  These data demonstrate ethanol-induced changes in both HPG and HPA activity that are estrous phase-specific, and support the possibility that changes in HPA activity in E females may reflect differential sensitivity to ovarian steroids. E females appear to have an increased HPA sensitivity to E(2), and a possible shift toward AVP regulation of HPA activity. That PF were similar to E females on some measures suggests that nutritional effects of diet or food restriction played a role in mediating at least some of the changes observed.
authors.affiliation: Department of Cellular and Physiological Sciences, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada.
authors.forename: Ni
authors.initials: N
authors.lastname: Lan
authors.forename: Fiona
authors.initials: F
authors.lastname: Yamashita
authors.forename: Alison G
authors.initials: AG
authors.lastname: Halpert
authors.forename: Joanna H
authors.initials: JH
authors.lastname: Sliwowska
authors.forename: Victor
authors.initials: V
authors.lastname: Viau
authors.forename: Joanne
authors.initials: J
authors.lastname: Weinberg
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood; D002492:Central Nervous System Depressants / Q000494:pharmacology / Q000633:toxicity*; D003345:Corticosterone / Q000097:blood; D004958:Estradiol / Q000097:blood; D030762:Estrous Cycle / Q000187:drug effects / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology / Q000633:toxicity*; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D023421:Models, Animal; D010053:Ovary / Q000187:drug effects / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000503:physiopathology*; D011374:Progesterone / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002492:Central Nervous System Depressants; D001127:Arginine Vasopressin; D000431:Ethanol; D011374:Progesterone; D004958:Estradiol; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D003345:Corticosterone