Document Detail


Prenatal blockade of estradiol synthesis impairs respiratory and metabolic responses to hypoxia in newborn and adult rats.
MedLine Citation:
PMID:  15142837     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We tested the hypothesis that estradiol modifies respiratory control in pregnant rats and participates in the development of respiratory chemoreflexes in fetuses. Pregnant rats (n = 12) received daily subcutaneous injections of vehicle (Veh, n = 6) or 4-androsten-4-ol-3,17-dione acetate (ATD; inhibitor of estradiol synthesis; n = 6; 5 mg/day in vehicle) from gestational day 16 (G16) to delivery. Baseline ventilation (whole body plethysmography) and metabolic rate [oxygen consumption (Vo(2))] were determined at G14 and G20, in pups [on postnatal day 3 (P3) and P20] and in adult rats (on P70) born to Veh- or ATD-treated mothers. Hypoxic chemoreflex was assessed in P3 rats by acute exposure to 60% O(2) and in P20 or P70 rats by moderate hypoxia (12% O(2), 30 min). ATD treatment reduced circulating estradiol in pregnant dams at G20 without producing changes in the circulating level of estradiol precursors (testosterone and androstenedione). ATD-treated dams showed impaired respiratory adjustment to late gestation. Pups born to ATD mothers had higher resting Vo(2) (+23% at P3, +21% at P20), respiratory frequency (+15% at P3, +12% at P20), and minute ventilation (+11% at P3, +18% at P20) than pups from Veh mothers. Respiratory decrease during acute hyperoxic exposure at P3 was -9.7% in Veh (P < 0.05 vs. room air) and only -2.6% (P = not significant) in ATD pups. In P20 ATD rats, hypoxic ventilatory response was attenuated compared with Veh. In P20 and P70 rats, the drop of Vo(2) in hypoxia (-31% in P70, P < 0.0001) was not observed in ATD rats. We conclude that estradiol secreted during late gestation is necessary for respiratory adjustment to pregnancy and is required for adequate development of respiratory and metabolic control in the offspring.
Authors:
V D Doan; S Gagnon; V Joseph
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-05-13
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  287     ISSN:  0363-6119     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-08-13     Completed Date:  2004-09-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R612-8     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Laval University, Centre de Recherche CHUQ, Hôpital St. François d'Assise, Local D0-711, 10 Rue de l'Espinay, G1L 3L5 Quebec, Quebec, Canada.
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MeSH Terms
Descriptor/Qualifier:
Adaptation, Physiological / drug effects
Aging*
Androstenedione / analogs & derivatives,  pharmacology
Animals
Animals, Newborn* / growth & development,  metabolism
Anoxia / metabolism,  physiopathology*
Estradiol / biosynthesis*
Estrogen Antagonists / pharmacology*
Female
Pregnancy
Prenatal Exposure Delayed Effects*
Rats
Rats, Sprague-Dawley
Respiration*
Chemical
Reg. No./Substance:
0/4-androsten-4-ol-3,17-dione; 0/Estrogen Antagonists; 50-28-2/Estradiol; 63-05-8/Androstenedione

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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