Prenatal glucocorticoid exposure alters hypothalamic-pituitary-adrenal function in juvenile guinea pigs.
The neurodevelopmental consequences of prenatal glucocorticoid exposure are not well-understood, particularly in species that give birth to neuroanatomically mature offspring. In the present study, we hypothesised that repeated prenatal glucocorticoid administration would alter hypothalamo-pituitary-adrenal (HPA) function in juvenile guinea pig offspring. Pregnant guinea pigs were injected with betamethasone (1 mg/kg) or vehicle on gestational days 40, 41, 50, 51, 60 and 61 (six doses). Prenatal glucocorticoid exposure abolished the pituitary-adrenal response to maternal separation in juvenile males, but had no effect in female offspring. Indeed, female offspring (vehicle and betamethasone) did not mount a significant HPA response to separation at 10 days of age. Although there were no effects of prenatal glucocorticoid exposure on hippocampal or hypothalamic corticosteroid receptor expression or corticotrophin-releasing factor (CRF) mRNA, there were significant effects in the pituitary and adrenal; again males were more affected than females. Prenatal glucocorticoid exposure increased pituitary pro-opiomelanocortin and CRF receptor mRNA, and markedly decreased adrenocortical CYP17 mRNA. In conclusion, repeated prenatal glucocorticoid exposure has profound influences on HPA function and regulation in the juvenile guinea pig, and this involves altered regulation at the level of the pituitary and adrenal cortex. Furthermore, juvenile males appear to be more vulnerable to the effects of prenatal glucocorticoid exposure than females.
Owen
D
D
Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Matthews
S G
SG
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D001623:Betamethasone / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D004334:Drug Administration Schedule; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006168:Guinea Pigs; D006624:Hippocampus / Q000378:metabolism; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D008426:Maternal Deprivation; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism; D012737:Sex Factors; D012934:Social Isolation; D018709:Statistics, Nonparametric; D013315:Stress, Psychological / Q000503:physiopathology*
D005938:Glucocorticoids; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D011987:Receptors, Steroid; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D001623:Betamethasone; D006854:Hydrocortisone