Changes in ovine fetal adrenocortical responsiveness after long-term hypoxemia.
This study tested the hypothesis that in the fetus long-term hypoxemia induces premature adrenocortical maturation and augments adrenal responsiveness to adrenocorticotropin hormone (ACTH). Pregnant ewes were exposed to high altitude (3,820 m) from 30 to 120 days gestation, when surgery was performed. Maternal arterial pressure of O2 (PaO2) was maintained at approximately 60 Torr by N2 infusion through a tracheal catheter. Fetal PaO2 was significantly lower in the hypoxemic (21 +/- 0.2 Torr) vs. normoxic (26 +/- 0.4 Torr) fetuses (P < 0.01). Between 125 and 140 days, basal ACTH and cortisol concentrations were similar in both groups. To assess changes in adrenal responsiveness, we challenged the fetuses with ACTH (100 ng/kg body wt, iv bolus) at 126 and 136 days. At 126 days, after ACTH challenge, fetal plasma ACTH peaked at similar values (275 +/- 43 and 250 +/- 26 pg/ml) in normoxic and hypoxemic fetuses, respectively. Plasma cortisol subsequently increased to 84 +/- 8 and 44 +/- 6 ng/ml in these groups. At 136 days, after ACTH challenge, plasma ACTH peaked at 379 +/- 57 and 336 +/- 21 pg/ml in normoxic and hypoxemic fetuses, respectively. Although plasma cortisol concentration in normoxic fetuses increased to 180 +/- 21 ng/ml, levels in hypoxemic fetuses only reached 62 +/- 12 ng/ml (P < 0.05 compared with normoxic). Catecholamine concentrations were not significantly different between the two groups. These data do not support the hypothesis that adrenocortical maturation occurs prematurely, augmenting adrenal responsiveness to ACTH after exposure to long-term hypoxemia. Rather, the ability of the fetus to respond to an ACTH challenge is blunted.
Department of Physiology, School of Medicine, Loma Linda University, California 92350.
L M
LM
Harvey
R D
RD
Gilbert
L D
LD
Longo
C A
CA
Ducsay
D000302:Adrenal Cortex / Q000187:drug effects / Q000196:embryology* / Q000503:physiopathology; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000818:Animals; D003366:Cosyntropin / Q000494:pharmacology*; D004837:Epinephrine / Q000097:blood; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005311:Fetal Hypoxia / Q000503:physiopathology*; D005333:Fetus / Q000502:physiology; D005865:Gestational Age; D006854:Hydrocortisone / Q000097:blood*; D000860:Hypoxia / Q000503:physiopathology*; D009638:Norepinephrine / Q000097:blood; D011247:Pregnancy; D012016:Reference Values; D012756:Sheep
D003366:Cosyntropin; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine