Periconceptional undernutrition in sheep accelerates maturation of the fetal hypothalamic-pituitary-adrenal axis in late gestation.
We investigated the effects of moderate maternal periconceptional undernutrition from 60 d before to 30 d after mating on fetal hypothalamic-pituitary-adrenal axis function in late gestation. Ewes were sampled regularly during the period of undernutrition for circulating hormone levels. Vascular catheters were inserted into ewes and their singleton fetuses at 112 d gestation (term, 145 d), and fetal ACTH(1-24) and metyrapone challenge tests were performed at 127 and 128 d. Postmortems were performed at 132 d. Fetuses of undernourished ewes (UN, n = 12) had elevated baseline cortisol concentrations (P < 0.05), compared with fetuses of ad libitum-fed ewes (n = 10). There were no differences between groups in fetal responses to ACTH challenge, but only UN fetuses demonstrated ACTH and 11-deoxycortisol responses to metyrapone (P < 0.05). UN fetuses had increased mRNA levels for proopiomelanocortin and prohormone convertase-1, but not -2, in the pars intermedia of the pituitary gland (P < 0.05). Glucocorticoid receptor mRNA levels were not different between groups in pituitary or hypothalamus. Maternal cortisol and ACTH levels during undernutrition were profoundly suppressed (P < 0.001), rather than elevated, in UN ewes. Furthermore, the normal pregnancy rise in maternal serum progesterone concentrations was delayed in undernourished mothers. These data demonstrate that events around the time of conception have profound effects on fetal hypothalamic-pituitary-adrenal development in late gestation and that factors other than fetal exposure to excess glucocorticoids may be important.
Bloomfield
Frank H
FH
Liggins Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand. f.bloomfield@auckland.ac.nz.
Oliver
Mark H
MH
Hawkins
Paul
P
Holloway
Alison C
AC
Campbell
Melanie
M
Gluckman
Peter D
PD
Harding
Jane E
JE
Challis
John R G
JR
D000311:Adrenal Glands / Q000033:anatomy & histology / Q000196:embryology; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics; D003346:Corticotropin-Releasing Hormone / Q000235:genetics; D005260:Female; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000196:embryology* / Q000502:physiology*; D017403:In Situ Hybridization; D009929:Organ Size; D010913:Pituitary-Adrenal System / Q000196:embryology* / Q000502:physiology*; D010927:Placental Insufficiency / Q000503:physiopathology*; D011247:Pregnancy; D011374:Progesterone / Q000097:blood; D012756:Sheep
D001127:Arginine Vasopressin; D011374:Progesterone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone