Maternal glucocorticoid treatment programs pituitary-adrenal regulation in adult offspring: sex-specific effects. Liu, Li, Antai Li, and Stephen G. Matthews. Departments of Physiology and Obstetrics and Gynecology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada
APStracts 8:0021E, 2001.
Pregnant guinea pigs were treated with dexamethasone (1 mg/kg) or vehicle on days 40- 41, days 50-51, and days 60-61 of gestation. At weaning, adult offspring were split into two groups. Group 1 guinea pigs were catheterized, and the hypothalamo-pituitary- adrenal (HPA) axis was tested in basal and activated states. Group 2 guinea pigs were euthanized with no further manipulation. In male offspring, prenatal dexamethasone exposure resulted in a significant reduction in brain-to-body weight ratio. Dexamethasone-exposed male offspring exhibited reduced basal and activated plasma cortisol levels, which was associated with elevated hippocampal mineralocorticoid receptor (MR) mRNA and increased plasma testosterone. In females exposed to glucocorticoids in utero, basal and stimulated plasma cortisol levels were higher in the follicular and/or late luteal phase of the cycle, but this effect was reversed in the late luteal phase, indicating a significant interaction of sex steroids. In female offspring (at estrous), glucocorticoid receptor mRNA levels were lower in the paraventricular nucleus and pars distalis but higher in the hippocampus in animals exposed to dexamethasone in utero. Hippocampal MR mRNA levels were significantly lower (~50%) than controls. In conclusion, repeated antenatal glucocorticoid treatment programs HPA function in a sex- specific manner, and these changes are associated with modification of corticosteroid receptor expression in the adult brain and pituitary. 

Received 28 August 2000; accepted in final form 20 January 2001
APS Manuscript Number E403-0.
Article publication pending Am J Physiol Endocrinol Metab
ISSN 1080-4757 Copyright 2001 The American Physiological Society.
Published in APStracts on 27 February 2001