L. Liu et al., Maternal glucocorticoid treatment programs HPA regulation in adult offspring: sex-specific effects, AM J P-ENDO, 280(5), 2001, pp. E729-E739
Citations number
34
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Pregnant guinea pigs were treated with dexamethasone (1 mg/kg) or vehicle o
n days 40-41, days 50-51, and days 60-61 of gestation. Adult offspring were
split into two groups. Group 1 guinea pigs were catheterized, and the hypo
thalamo-pituitary-adrenal (HPA) axis was tested in basal and activated stat
es. Group 2 guinea pigs were euthanized with no further manipulation. In ma
le offspring, prenatal dexamethasone exposure resulted in a significant red
uction in brain-to-body weight ratio. Dexamethasone-exposed male offspring
exhibited reduced basal and activated plasma cortisol levels, which was ass
ociated with elevated hippocampal mineralocorticoid receptor (MR) mRNA and
increased plasma testosterone. In females exposed to glucocorticoids in ute
ro, basal and stimulated plasma cortisol levels were higher in the follicul
ar and early luteal phases of the cycle, but this effect was reversed in th
e late luteal phase, indicating a significant interaction of sex steroids.
In female offspring (at estrus), glucocorticoid receptor mRNA levels were l
ower in the paraventricular nucleus and pars distalis but higher in the hip
pocampus in animals exposed to dexamethasone in utero. Hippocampal MR mRNA
levels were significantly lower (similar to 50%) than in controls. In concl
usion, 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.