Sexually dimorphic effects of alcohol exposure in utero on neuroendocrine and immune functions in chronic alcohol-exposed adult rats

Ildiko Halasz, Fraser Aird, Lifang Li, Michael B. Prystowsky, Eva Redei

Research output: Contribution to journalArticle

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Abstract

Maternal ethanol consumption has deleterious effects on the offspring's neuroendocrine and T-cell-dependent functions. Chronic alcohol consumption in adulthood has also been associated with activated hypothalamic-pituitary-adrenal (HPA) function and immunosuppression which is demonstrable at the T-cell level. Our aim was to establish whether prenatal alcohol exposure alters the neuroendocrine and immune responses to chronic alcohol challenge in adult male and female offspring. Adult male rats placed on a liquid alcohol diet for 5 weeks had significantly decreased thymus weight, hypertrophied adrenals, and elevated plasma ACTH and corticosterone levels. Splenic lymphocyte Concanavalin A (Con A)-stimulated proliferation in the ethanol-treated rats was decreased compared to that in pair-fed controls. Thus, prolonged alcohol exposure activated the HPA axis and suppressed T-cell function. The effects of prenatal alcohol exposure, as a predispositional factor, on the HPA axis and on the T-cell functions of adult chronic alcohol-exposed rats were examined in the offspring of dams fed ethanol (FAE) or an isocaloric liquid (PF) diet during the last 2 weeks of gestation. The adult offspring of both sexes and prenatal treatment groups were then placed on an alcohol-containing liquid diet for 5 weeks. Fetal alcohol exposure decreased anterior pituitary proopiomelanocortin mRNA levels and increased glucocorticoid receptor (GR) mRNA levels in males and decreased GR mRNA levels in females. There were no differences in hypothalamic CRF mRNA and GR mRNA levels between the prenatal treatment groups. There was no significant difference in Con A-stimulated lymphocyte proliferation between FAE and PF males. However, FAE females showed Con A-stimulated lymphocyte proliferation significantly higher than those of all other groups, including pair-fed females. Prostaglandin E2 (PGE2) suppressed lymphocyte proliferation to a lesser degree in FAE males than in any other group. Furthermore, T-cell response to Con A was enhanced by indomethacin, a prostaglandin biosynthesis inhibitor, in FAE males suggesting that increased prostaglandin synthesis may occur in FAE males after chronic alcohol exposure. Increased levels of endogenous PGE2 could also be inferred from the enhanced levels of interleukin-2 receptor α (IL-2Rα) mRNA in activated lymphocytes of male but not of female FAE offspring compared to PF. In summary, the results of this study demonstrate that prenatal alcohol exposure leads to a specific HPA-related vulnerability in males to the deleterious effects of ethanol in adulthood. Although prenatal alcohol did not further aggravate the effects of chronic alcohol exposure on lymphocyte proliferation response to Con A in adult male offspring, altered T-cell responses could be unmasked.

Original languageEnglish (US)
Pages (from-to)343-353
Number of pages11
JournalMolecular and Cellular Neuroscience
Volume4
Issue number4
StatePublished - 1993
Externally publishedYes

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Alcohols
Concanavalin A
Lymphocytes
T-Lymphocytes
Messenger RNA
Glucocorticoid Receptors
Ethanol
Diet
Dinoprostone
Corticotropin-Releasing Hormone Receptors
Prostaglandin Antagonists
Neuroendocrine Cells
Pro-Opiomelanocortin
Interleukin-2 Receptors
Corticosterone
Indomethacin
Alcohol Drinking
Adrenocorticotropic Hormone
Immunosuppression
Thymus Gland

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

Cite this

Sexually dimorphic effects of alcohol exposure in utero on neuroendocrine and immune functions in chronic alcohol-exposed adult rats. / Halasz, Ildiko; Aird, Fraser; Li, Lifang; Prystowsky, Michael B.; Redei, Eva.

In: Molecular and Cellular Neuroscience, Vol. 4, No. 4, 1993, p. 343-353.

Research output: Contribution to journalArticle

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AU - Prystowsky, Michael B.

AU - Redei, Eva

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