Abstract
We have experimentally restricted placental growth in the sheep to investigate the impact of reduced substrate delivery on fetal pituitary proopiomelanocortin (POMC) mRNA levels and on circulating ACTH 1-39, immunoreactive ACTH, and cortisol concentrations during late gestation. Endometrial caruncles were removed in nine ewes before mating to reduce the number of placentomes formed [placental restriction group (PR)]. Fetal arterial PO2 and O2 saturation were reduced in the PR group (2.0 ± 0.1 kPa and 42.8 ± 1.1%, n = 9) when compared with control fetuses (3.1 ± 0.1 kPa and 66.4 ± 0.9%, n = 10). The ratio of anterior pituitary POMC mRNA:18 S ribosomal RNA was also lower (p < 0.05) in the PR group (0.49 ± 0.05) when compared with the control group (0.80 ± 0.12) after 140 d of gestation. In contrast, plasma concentrations of ACTH 1-39 and immunoreactive ACTH were similar in the PR and control groups throughout late gestation. Plasma ACTH 1-39 concentrations increased (p < 0.0116) between 128 and 134 d of gestation, in both the PR (122-128 d: 2.70 ± 0.34 pmol/L: 134-141 d; 7.07 ± 1.57 pmol/L) and control (122-128 d; 3.36 ± 0.56 pmol/L: 134-141 d; 10.78 ± 2.88 pmol/L) groups. Combined adrenal weight was higher (p < 0.005) in the PR group (130 ± 10 mg/kg) compared with controls (80 ± 1 mg/kg) at 140 d of gestation, and plasma cortisol concentrations were also higher (p < 0.02) in PR than control fetuses between 127 and 141 d of gestation. These changes imply that the fetal hypothalamo-pituitary-adrenal axis is operating at a new central set point in the growth-restricted fetus.
| Original language | English |
|---|---|
| Pages (from-to) | 861-866 |
| Number of pages | 6 |
| Journal | Pediatric Research |
| Volume | 40 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 1 Jan 1996 |
| Externally published | Yes |
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Placental restriction alters the functional development of the pituitary-adrenal axis in the sheep fetus during late gestation. / Phillips, Ian D.; Simonetta, Giuseppe; Owens, Julie A.; Robinson, Jeffrey S.; Clarke, Iain J.; McMillen, I. Caroline.
In: Pediatric Research, Vol. 40, No. 6, 01.01.1996, p. 861-866.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Placental restriction alters the functional development of the pituitary-adrenal axis in the sheep fetus during late gestation
AU - Phillips, Ian D.
AU - Simonetta, Giuseppe
AU - Owens, Julie A.
AU - Robinson, Jeffrey S.
AU - Clarke, Iain J.
AU - McMillen, I. Caroline
PY - 1996/1/1
Y1 - 1996/1/1
N2 - We have experimentally restricted placental growth in the sheep to investigate the impact of reduced substrate delivery on fetal pituitary proopiomelanocortin (POMC) mRNA levels and on circulating ACTH 1-39, immunoreactive ACTH, and cortisol concentrations during late gestation. Endometrial caruncles were removed in nine ewes before mating to reduce the number of placentomes formed [placental restriction group (PR)]. Fetal arterial PO2 and O2 saturation were reduced in the PR group (2.0 ± 0.1 kPa and 42.8 ± 1.1%, n = 9) when compared with control fetuses (3.1 ± 0.1 kPa and 66.4 ± 0.9%, n = 10). The ratio of anterior pituitary POMC mRNA:18 S ribosomal RNA was also lower (p < 0.05) in the PR group (0.49 ± 0.05) when compared with the control group (0.80 ± 0.12) after 140 d of gestation. In contrast, plasma concentrations of ACTH 1-39 and immunoreactive ACTH were similar in the PR and control groups throughout late gestation. Plasma ACTH 1-39 concentrations increased (p < 0.0116) between 128 and 134 d of gestation, in both the PR (122-128 d: 2.70 ± 0.34 pmol/L: 134-141 d; 7.07 ± 1.57 pmol/L) and control (122-128 d; 3.36 ± 0.56 pmol/L: 134-141 d; 10.78 ± 2.88 pmol/L) groups. Combined adrenal weight was higher (p < 0.005) in the PR group (130 ± 10 mg/kg) compared with controls (80 ± 1 mg/kg) at 140 d of gestation, and plasma cortisol concentrations were also higher (p < 0.02) in PR than control fetuses between 127 and 141 d of gestation. These changes imply that the fetal hypothalamo-pituitary-adrenal axis is operating at a new central set point in the growth-restricted fetus.
AB - We have experimentally restricted placental growth in the sheep to investigate the impact of reduced substrate delivery on fetal pituitary proopiomelanocortin (POMC) mRNA levels and on circulating ACTH 1-39, immunoreactive ACTH, and cortisol concentrations during late gestation. Endometrial caruncles were removed in nine ewes before mating to reduce the number of placentomes formed [placental restriction group (PR)]. Fetal arterial PO2 and O2 saturation were reduced in the PR group (2.0 ± 0.1 kPa and 42.8 ± 1.1%, n = 9) when compared with control fetuses (3.1 ± 0.1 kPa and 66.4 ± 0.9%, n = 10). The ratio of anterior pituitary POMC mRNA:18 S ribosomal RNA was also lower (p < 0.05) in the PR group (0.49 ± 0.05) when compared with the control group (0.80 ± 0.12) after 140 d of gestation. In contrast, plasma concentrations of ACTH 1-39 and immunoreactive ACTH were similar in the PR and control groups throughout late gestation. Plasma ACTH 1-39 concentrations increased (p < 0.0116) between 128 and 134 d of gestation, in both the PR (122-128 d: 2.70 ± 0.34 pmol/L: 134-141 d; 7.07 ± 1.57 pmol/L) and control (122-128 d; 3.36 ± 0.56 pmol/L: 134-141 d; 10.78 ± 2.88 pmol/L) groups. Combined adrenal weight was higher (p < 0.005) in the PR group (130 ± 10 mg/kg) compared with controls (80 ± 1 mg/kg) at 140 d of gestation, and plasma cortisol concentrations were also higher (p < 0.02) in PR than control fetuses between 127 and 141 d of gestation. These changes imply that the fetal hypothalamo-pituitary-adrenal axis is operating at a new central set point in the growth-restricted fetus.
UR - http://www.scopus.com/inward/record.url?scp=0029825371&partnerID=8YFLogxK
U2 - 10.1203/00006450-199612000-00014
DO - 10.1203/00006450-199612000-00014
M3 - Article
C2 - 8947963
AN - SCOPUS:0029825371
VL - 40
SP - 861
EP - 866
JO - Pediatric Research
JF - Pediatric Research
SN - 0031-3998
IS - 6
ER -