Effects of Prenatal Ethanol Exposure on Hypothalamic-Pituitary-Adrenal Function Across the Estrous Cycle

Authors

  • Ni Lan,

    1. From the Department of Cellular and Physiological Sciences, University of British Columbia (NL, FY, AGH, JHS, VV, JW), Vancouver, British Columbia, Canada; and Department of Anatomy, College of Basic Medical Sciences, China Medical University (NL), Shenyang, Liaoning, China.
    Search for more papers by this author
  • Fiona Yamashita,

    1. From the Department of Cellular and Physiological Sciences, University of British Columbia (NL, FY, AGH, JHS, VV, JW), Vancouver, British Columbia, Canada; and Department of Anatomy, College of Basic Medical Sciences, China Medical University (NL), Shenyang, Liaoning, China.
    Search for more papers by this author
  • Alison G. Halpert,

    1. From the Department of Cellular and Physiological Sciences, University of British Columbia (NL, FY, AGH, JHS, VV, JW), Vancouver, British Columbia, Canada; and Department of Anatomy, College of Basic Medical Sciences, China Medical University (NL), Shenyang, Liaoning, China.
    Search for more papers by this author
  • Joanna H. Sliwowska,

    1. From the Department of Cellular and Physiological Sciences, University of British Columbia (NL, FY, AGH, JHS, VV, JW), Vancouver, British Columbia, Canada; and Department of Anatomy, College of Basic Medical Sciences, China Medical University (NL), Shenyang, Liaoning, China.
    Search for more papers by this author
  • Victor Viau,

    1. From the Department of Cellular and Physiological Sciences, University of British Columbia (NL, FY, AGH, JHS, VV, JW), Vancouver, British Columbia, Canada; and Department of Anatomy, College of Basic Medical Sciences, China Medical University (NL), Shenyang, Liaoning, China.
    Search for more papers by this author
  • Joanne Weinberg

    1. From the Department of Cellular and Physiological Sciences, University of British Columbia (NL, FY, AGH, JHS, VV, JW), Vancouver, British Columbia, Canada; and Department of Anatomy, College of Basic Medical Sciences, China Medical University (NL), Shenyang, Liaoning, China.
    Search for more papers by this author

Reprint requests: Joanne Weinberg, PhD, Department of Cellular and Physiological Sciences, 2350 Health Sciences Mall, University of British Columbia, Vancouver, BC, V6T 1Z3 Canada; Fax: 604-822-2316; E-mail: jweinberg@exchange.ubc.ca

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 (E2) 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 E2, 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.

Ancillary