Developmental programming of adult adrenal structure and steroidogenesis: effects of fetal glucocorticoid excess and postnatal dietary omega-3 fatty acids.
Fetal glucocorticoid excess programs a range of detrimental outcomes in the adult phenotype, at least some of which may be due to altered adult adrenocortical function. In this study, we determined the effects of maternal dexamethasone treatment on offspring adrenal morphology and function, as well as the interactive effects of postnatal dietary omega-3 (n-3) fatty acids. This postnatal dietary intervention has been shown to alleviate many of the programming outcomes in this model, but whether this is via the effects on adrenal function is unknown. Dexamethasone acetate was administered to pregnant rats (0.75 microg/ml drinking water) from day 13 to term. Cross-fostered offspring were raised on either a standard or high-n-3 diet. Adrenal weight (relative to body weight) at 6 months of age was unaffected by prenatal dexamethasone, regardless of postnatal diet, and stereological analysis showed no effect of dexamethasone on the volumes of adrenal components (zona glomerulosa, zona fasciculata/reticularis or adrenal medulla). Expression of key steroidogenic genes (Cyp11a1 and Star) was unaffected by either prenatal dexamethasone or postnatal diet. In contrast, adrenal expression of Mc2r mRNA, which encodes the ACTH receptor, was higher in offspring of dexamethasone-treated mothers, an effect partially attenuated by the Hn3 diet. Moreover, stress-induced levels of plasma and urinary corticosterone and urinary aldosterone were elevated in offspring of dexamethasone-treated mothers, indicative of enhanced adrenal responsiveness. In conclusion, this study shows that prenatal exposure to dexamethasone does not increase basal adrenocortical activity but does result in a more stress-responsive adrenal phenotype, possibly via increased Mc2r expression.
Waddell
Brendan J
BJ
School of Anatomy and Human Biology, The University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia 6009, Australia. bwaddell@anhb.uwa.edu.au
Bollen
Maike
M
Wyrwoll
Caitlin S
CS
Mori
Trevor A
TA
Mark
Peter J
PJ
D000311:Adrenal Glands / Q000254:growth & development* / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects*; D004042:Dietary Fats, Unsaturated / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005333:Fetus / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D018811:Maternal Exposure; D009929:Organ Size; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013256:Steroids / Q000097:blood / Q000652:urine
D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D005938:Glucocorticoids; D013256:Steroids; D003907:Dexamethasone; D002786:Cholesterol Side-Chain Cleavage Enzyme