Endocrinology, Vol 133, 452-460, Copyright © 1993 by Endocrine Society

ARTICLES

Maternal adrenalectomy alters the immune and endocrine functions of fetal alcohol-exposed male offspring

E Redei, I Halasz, LF Li, MB Prystowsky and F Aird
Department of Psychiatry, University of Pennsylvania, Philadelphia 19104.

Exposure to ethanol in utero compromises the offspring's developing immune and endocrine systems. Persistent functional changes, particularly in T-cell-dependent aspects of immunity and in hypothalamic-pituitary-adrenal activity, are commonly seen. The present study examined the degree to which fetal alcohol exposure (FAE) during development suppressed the lymphocyte proliferative response to Concanavalin-A (Con A). We also examined the effect of maternal adrenalectomy on the expression of glucocorticoid-regulated genes and the response to Con A in FAE offspring. Con A-stimulated lymphocyte proliferation was stably suppressed (between 28-46%) in FAE males compared to isocalorically pair-fed offspring at 7, 21, 40, and 60 days of age. In contrast, lymphocyte proliferation in the immature or peripubertal FAE female was totally unaffected. In 60-day- old male rats, maternal adrenalectomy reversed the FAE-induced suppression of Con A-stimulated proliferation, but had no effect on lymphocyte proliferation. FAE increased anterior pituitary POMC (the precursor of ACTH) mRNA levels dramatically in males, and this increase was also reversed by maternal adrenalectomy. In both sexes, anterior pituitary glucocorticoid receptor mRNA levels were unaffected by prenatal alcohol exposure alone, but were significantly decreased in male and increased in female offspring of adrenalectomized dams ingesting alcohol. Furthermore, in male, but not female, offspring, hypothalamic levels of glucocorticoid receptor and CRF mRNA were increased significantly by FAE alone or in combination with maternal adrenalectomy. In female, but not male, offspring, maternal adrenalectomy with concomitant alcohol exposure increased anterior pituitary POMC mRNA levels compared to that in sham/pair-fed offspring. In summary, FAE induced a gender-specific impairment of Con A-stimulated lymphocyte proliferation. This deficit is present both before and after puberty, demonstrating its stability into adulthood. Furthermore, in males, maternal adrenalectomy reversed these FAE-induced deficits in T-cell function as well as the effect of FAE on anterior pituitary POMC expression. This supports the hypothesis that maternal adrenal hormones participate in the immunosuppressive "imprinting" of the FAE fetus and are, therefore, causally implicated in the sexually dimorphic T-cell dysfunction found in FAE offspring.

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