title: A short period of maternal nutrient restriction in late gestation modifies pituitary-adrenal function in adult guinea pig offspring.
abstract: Altered fetal environment can program the hypophyseal-pituitary-adrenal (HPA) axis development and thus affect endocrine function in later life. We hypothesized that 48 h of maternal nutrient restriction during the period of maximal fetal brain growth alters HPA function in adult offspring and leads to modified blood pressure regulation. Pregnant guinea pigs (n = 15) were deprived of food (water ad libitum) or fed normally (n = 13) on days 50 and 51 of gestation, after which they were all fed normally (birth = 68 days). Carotid artery and jugular vein catheters were implanted in adult guinea pig offspring (day 65). Animals were treated with corticotropin (ACTH(1-24); 0.5 microg/kg), corticotropin-releasing hormone (CRH; 0.5 microg/kg) and insulin (5 units/kg), and pituitary-adrenal responses were measured. Guinea pigs were then euthanized and pituitaries removed for analysis of pro-opiomelanocortin (POMC) and glucocorticoid receptor (GR) mRNA levels. There was no effect of prenatal treatment on body weight, blood pressure or heart rate. In male offspring, both basal ACTH (p < 0.007) and basal cortisol (p < 0.05) levels were significantly reduced in animals whose mothers had been nutrient restricted (NR). In contrast, in female offspring, basal plasma ACTH was not different between offspring from NR mothers and controls; however, basal plasma cortisol concentrations were significantly (p < 0.01) elevated at 13.00 h in females born to NR mothers. Responses to HPA challenge were different between offspring from NR mothers and control offspring, and these differences were consistent with alterations in basal adrenocortical function. There was no effect of prenatal treatment on POMC mRNA levels in the pars distalis or pars intermedia. However, GR mRNA levels were significantly (p < 0.05) reduced in adult female offspring born to NR mothers. In conclusion, 48 h of maternal nutrient restriction during pregnancy has a long-term effect on HPA function in adult offspring, and this effect is highly sex specific, but does not result in alteration of blood pressure.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ont., Canada.
authors.forename: R I
authors.initials: RI
authors.lastname: Lingas
authors.forename: S G
authors.initials: SG
authors.lastname: Matthews
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000494:pharmacology; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D005260:Female; D005508:Food Deprivation; D005865:Gestational Age; D006168:Guinea Pigs; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010902:Pituitary Gland / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011333:Pro-Opiomelanocortin / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000235:genetics
chemical_list: D007328:Insulin; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone