Tags

Type your tag names separated by a space and hit enter

Effects of prenatal ethanol exposure on basal limbic-hypothalamic-pituitary-adrenal regulation: role of corticosterone.
Alcohol Clin Exp Res 2007; 31(9):1598-610AC

Abstract

BACKGROUND

Rats prenatally exposed to ethanol (E) exhibit hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness and changes in central HPA regulation following exposure to stressors. Whether ethanol-induced alterations in basal HPA regulation play a role in mediating HPA hyperresponsiveness remains unclear. We utilized adrenalectomy (ADX), with or without corticosterone (CORT) replacement, to investigate basal HPA function and the role of CORT in mediating ethanol-induced alterations.

METHODS

Adult males and females from prenatal E, pair-fed (PF), and ad lib-fed control (C) groups were terminated at the circadian peak, 7 days following sham surgery or ADX, with or without CORT replacement. Plasma levels of CORT and adrenocorticotropin (ACTH), and mRNA levels of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) in the paraventricular nucleus, CRH Type 1 receptor (CRH-R1) and pro-opiomelanocortin (POMC) in the anterior pituitary, and mineralocorticoid (MR) and glucocorticoid (GR) receptors in the dorsal hippocampus were determined.

RESULTS

Adrenalectomy resulted in significantly greater plasma ACTH elevations in E and PF males, and parallel CRH mRNA elevations in both E and PF males and females compared with their C counterparts. In contrast, pituitary CRH-R1 mRNA levels were lower in E compared with C males, with no differences in POMC. In addition, in response to ADX, E females showed a greater MR mRNA response, and E males showed a greater GR mRNA response compared with their C counterparts, and CORT replacement was ineffective in normalizing ADX-induced alterations in ACTH levels in E and PF females, hippocampal MR mRNA levels in E males, and AVP mRNA levels in PF males and females.

CONCLUSIONS

Together, these data indicate that the prenatal ethanol exposure induces HPA dysregulation under basal conditions at multiple levels of the axis, resulting in alterations in both HPA drive and feedback regulation and/or in the balance between drive and feedback. While some effects may be nutritionally mediated, it appears that the mechanisms underlying basal HPA dysregulation may differ between E and PF animals rather than occurring along a continuum of effects on the same pathway. Altered basal HPA tone may play a role in mediating the HPA hyperresponsiveness to stressors observed in E offspring.

Authors+Show Affiliations

Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17760789

Citation

Glavas, Maria M., et al. "Effects of Prenatal Ethanol Exposure On Basal Limbic-hypothalamic-pituitary-adrenal Regulation: Role of Corticosterone." Alcoholism, Clinical and Experimental Research, vol. 31, no. 9, 2007, pp. 1598-610.
Glavas MM, Ellis L, Yu WK, et al. Effects of prenatal ethanol exposure on basal limbic-hypothalamic-pituitary-adrenal regulation: role of corticosterone. Alcohol Clin Exp Res. 2007;31(9):1598-610.
Glavas, M. M., Ellis, L., Yu, W. K., & Weinberg, J. (2007). Effects of prenatal ethanol exposure on basal limbic-hypothalamic-pituitary-adrenal regulation: role of corticosterone. Alcoholism, Clinical and Experimental Research, 31(9), pp. 1598-610.
Glavas MM, et al. Effects of Prenatal Ethanol Exposure On Basal Limbic-hypothalamic-pituitary-adrenal Regulation: Role of Corticosterone. Alcohol Clin Exp Res. 2007;31(9):1598-610. PubMed PMID: 17760789.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of prenatal ethanol exposure on basal limbic-hypothalamic-pituitary-adrenal regulation: role of corticosterone. AU - Glavas,Maria M, AU - Ellis,Linda, AU - Yu,Wayne K, AU - Weinberg,Joanne, PY - 2007/9/1/pubmed PY - 2007/10/17/medline PY - 2007/9/1/entrez SP - 1598 EP - 610 JF - Alcoholism, clinical and experimental research JO - Alcohol. Clin. Exp. Res. VL - 31 IS - 9 N2 - BACKGROUND: Rats prenatally exposed to ethanol (E) exhibit hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness and changes in central HPA regulation following exposure to stressors. Whether ethanol-induced alterations in basal HPA regulation play a role in mediating HPA hyperresponsiveness remains unclear. We utilized adrenalectomy (ADX), with or without corticosterone (CORT) replacement, to investigate basal HPA function and the role of CORT in mediating ethanol-induced alterations. METHODS: Adult males and females from prenatal E, pair-fed (PF), and ad lib-fed control (C) groups were terminated at the circadian peak, 7 days following sham surgery or ADX, with or without CORT replacement. Plasma levels of CORT and adrenocorticotropin (ACTH), and mRNA levels of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) in the paraventricular nucleus, CRH Type 1 receptor (CRH-R1) and pro-opiomelanocortin (POMC) in the anterior pituitary, and mineralocorticoid (MR) and glucocorticoid (GR) receptors in the dorsal hippocampus were determined. RESULTS: Adrenalectomy resulted in significantly greater plasma ACTH elevations in E and PF males, and parallel CRH mRNA elevations in both E and PF males and females compared with their C counterparts. In contrast, pituitary CRH-R1 mRNA levels were lower in E compared with C males, with no differences in POMC. In addition, in response to ADX, E females showed a greater MR mRNA response, and E males showed a greater GR mRNA response compared with their C counterparts, and CORT replacement was ineffective in normalizing ADX-induced alterations in ACTH levels in E and PF females, hippocampal MR mRNA levels in E males, and AVP mRNA levels in PF males and females. CONCLUSIONS: Together, these data indicate that the prenatal ethanol exposure induces HPA dysregulation under basal conditions at multiple levels of the axis, resulting in alterations in both HPA drive and feedback regulation and/or in the balance between drive and feedback. While some effects may be nutritionally mediated, it appears that the mechanisms underlying basal HPA dysregulation may differ between E and PF animals rather than occurring along a continuum of effects on the same pathway. Altered basal HPA tone may play a role in mediating the HPA hyperresponsiveness to stressors observed in E offspring. SN - 0145-6008 UR - https://www.unboundmedicine.com/medline/citation/17760789/Effects_of_prenatal_ethanol_exposure_on_basal_limbic_hypothalamic_pituitary_adrenal_regulation:_role_of_corticosterone_ L2 - https://doi.org/10.1111/j.1530-0277.2007.00460.x DB - PRIME DP - Unbound Medicine ER -