Pituitary-adrenal responses to acute hypoxemia during and after maternal dexamethasone treatment in sheep.
The effects of maternal dexamethasone treatment on hypothalamic-pituitary-adrenal axis function were determined during basal and hypoxemic conditions in maternal and fetal sheep. Under halothane, ewes and their fetuses were catheterized at 117 d gestation (term = 145 d). Starting at 124 d, the ewes received i.m. injections of two doses of either dexamethasone (12 mg) or saline at 24-h intervals. All animals experienced one episode of hypoxemia when the dexamethasone was present in the maternal and fetal circulations [125 +/- 1 d (H1)] and a second episode of hypoxemia when the steroid was no longer detectable in either the maternal or fetal circulations [128 +/- 1 d (H2)]. The fall in partial pressure of oxygen in arterial blood in response to hypoxia was similar in the two episodes in both the fetal and the maternal blood. Maternal dexamethasone treatment diminished maternal and fetal basal plasma cortisol but not ACTH during the normoxic period of H1 but not H2. In control animals, hypoxemia induced increases in fetal but not maternal ACTH and cortisol concentrations. In dexamethasone-treated animals, maternal ACTH and cortisol concentrations also remained unchanged from baseline in both H1 and H2. In contrast, fetal plasma ACTH and cortisol responses to hypoxemia were significantly suppressed during H1 but not H2. Correlation of fetal plasma ACTH and cortisol concentrations suggested diminished cortisol output without a change in adrenocortical responsiveness in dexamethasone-treated fetuses during H1 but not H2. Maternal treatment with dexamethasone transiently suppressed maternal and fetal basal hypothalamic-pituitary-adrenal axis function and the fetal plasma ACTH and cortisol responses to acute hypoxemia in sheep.
Department of Physiology, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.
Juanita K
JK
Jellyman
David S
DS
Gardner
Hugh H G
HH
McGarrigle
Abigail L
AL
Fowden
Dino A
DA
Giussani
D000208:Acute Disease; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000097:blood; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D010100:Oxygen / Q000097:blood; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000502:physiology*; D011247:Pregnancy; D012756:Sheep
D005938:Glucocorticoids; D002245:Carbon Dioxide; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D010100:Oxygen; D006854:Hydrocortisone