title: The impact of maternal overnutrition and obesity on hypothalamic-pituitary-adrenal axis response of offspring to stress.
abstract: We evaluated the effect of maternal obesity before and throughout gestation on offspring hypothalamic-pituitary-adrenal axis function. Multiparous Rambouillet by Columbia crossbred ewes were fed either 100% of National Research Council (NRC) recommendations (control, C) or 150% of NRC recommendations (obese, OB) from 60 d before mating until lambing. Ten lambs born to OB ewes (five males and five females), and eight lambs born to C ewes (three male and five female) were studied. From delivery to weaning lambs were maintained with their mothers, who were all fed 100% NRC recommendations. After weaning, all lambs were group housed and fed the same diet to meet NRC requirements. At 19 mo of age lambs were placed in individual pens and fed a pelletized diet to meet maintenance requirements. Jugular vein catheters were placed and 2 d later lambs received an intravenous (i.v.) adrenocorticotropic hormone (ACTH) challenge followed by an i.v. corticotropin-releasing hormone (CRH)/arginine vasopressin (AVP) challenge 1 d later. Thirty d later offspring were again catheterized and placed into metabolism crates for 2 d before receiving an isolation stress test. ACTH and cortisol responses to the isolation stress test and CRH/AVP challenge and cortisol responses to ACTH challenge were determined. Cortisol was quantified via radioimmunoassay and ACTH was quantified using an Immulite 1000; both were analyzed using repeated measures using the MIXED procedure of SAS. Offspring from OB ewes had elevated basal plasma ACTH and cortisol compared with C offspring before all three challenges (P < 0.05). Offspring from OB mothers tended (P = 0.06) to have a greater ACTH response after an i.v. CRH/AVP injection than offspring from C mothers (12,340 ± 1,430 vs 8,170 ± 1,570 area under the curve, respectively). Cortisol response to the CRH/AVP and ACTH challenges was not influenced by maternal nutrition (P = 0.46) and averaged 4.77 ± 0.2 μg/dL and 1.94 ± 0.01 μg/dL, respectively. The ACTH response following the isolation stress test was also similar (P = 0.82) for OB and C offspring (147 ± 20 pg/mL), and cortisol response during the isolation stress test was similar between C and OB offspring (P = 0.64, 5.25 ± 0.3 μg/dL). These findings suggest that maternal obesity before and during gestation does not affect stress responses by the offspring, but has an impact on hypothalamic-pituitary-adrenal sensitivity. The lack of differences in cortisol release under the influence of difference concentrations of ACTH during the CRH/AVP challenge could indicate adrenal dysfunction in OB offspring.
authors.affiliation: Center for the Study of Fetal Programming, Laramie, WY, USA.
authors.forename: N M
authors.initials: NM
authors.lastname: Long
authors.forename: P W
authors.initials: PW
authors.lastname: Nathanielsz
authors.forename: S P
authors.initials: SP
authors.lastname: Ford
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D019540:Area Under Curve; D001127:Arginine Vasopressin / Q000494:pharmacology; D001724:Birth Weight / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D005260:Female; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D016018:Least-Squares Analysis; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena / Q000502:physiology*; D009765:Obesity / Q000097:blood / Q000503:physiopathology*; D010913:Pituitary-Adrenal System / Q000502:physiology* / Q000503:physiopathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000503:physiopathology*; D012756:Sheep / Q000502:physiology*; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D001127:Arginine Vasopressin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone