Response to hemorrhagic stress in the rhesus monkey fetus in utero: effects on the pituitary-adrenal axis.
In human pregnancy, fetoplacental hemorrhage is often associated with morbidity and potentially mortality. We investigated the effect of acute fetal hemorrhage on the fetal pituitary-adrenal axis in the subhuman primate (Macaca mulatta). We measured fetal and maternal plasma concentrations of ACTH, cortisol, and dehydroepiandrosterone sulfate (DHAS) by RIA in 10 rhesus monkeys. At 133-158 days of gestation (d) the fetuses were subjected to acute hemorrhage (0.5 mL/min for 10 min). Fetal plasma ACTH and cortisol concentrations were significantly increased above baseline in response to fetal hemorrhage. There was a more rapid, but significantly reduced, fetal plasma ACTH and cortisol response in the 133-143 d fetuses than in the 147-158 d fetuses. In 133-143 d fetuses, the maximal changes from baseline in plasma ACTH and cortisol concentrations were +6.5 +/- 2.6 pmol/L at +25 min and +4.55 +/- 1.19 nmol/L at +10 min, respectively. Fetal plasma ACTH and cortisol concentrations remained elevated throughout the 60-min period after hemorrhage (3.06 +/- 1.21 pmol/L and +2.42 +/- 1.05 nmol/L at +70 min). In 147-158 d fetuses, the maximal changes from baseline in plasma ACTH and cortisol concentrations were +13.7 +/- 4.23 pmol/L and +12.92 +/- 3.25 nmol/L at +70 min. In the 133-143 d fetuses, plasma DHAS concentrations did not change in response to hemorrhage, whereas in the 147-158 d fetuses, plasma DHAS concentrations were elevated above baseline during the hemorrhage (+624.2 +/- 269.5 nmol/L, at +9 min) and returned quickly to pre-hemorrhage values. These data suggest that the fetal pituitary-adrenal axis plays a role in the fetal response to intrauterine stress, but that only later in gestation is the fetal cortisol response to fetal hemorrhage mediated via ACTH secreted by the fetal pituitary.
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco 94143-0556.
C L
CL
Coulter
M C
MC
Martin
C C
CC
Voytek
J I
JI
Hofmann
R B
RB
Jaffe
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate; D004622:Embryo, Mammalian / Q000502:physiology; D005312:Fetal Blood; D005315:Fetal Diseases / Q000097:blood / Q000503:physiopathology*; D006470:Hemorrhage / Q000097:blood / Q000150:complications*; D006854:Hydrocortisone / Q000097:blood; D008253:Macaca mulatta / Q000196:embryology*; D009994:Osmolar Concentration; D010913:Pituitary-Adrenal System; D013312:Stress, Physiological / Q000097:blood / Q000209:etiology* / Q000503:physiopathology*
D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone