Linked Life Data

8477651

Source:http://linkedlifedata.com/resource/pubmed/id/8477651

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1993-5-25
pubmed:databankReference
pubmed:abstractText
In fetal sheep, there is a concomitant prepartum rise in cortisol and corticosteroid-binding globulin (CBG) that maintains a low free plasma cortisol level and allows for a low negative feedback effect of cortisol on the secretion of ACTH from the fetal pituitary. However, the stimulus for the prepartum increase in CBG and the mechanism(s) of this effect are not known. It has been proposed that glucocorticoids increase CBG concentrations, and therefore, we infused fetal sheep with the synthetic glucocorticoid dexamethasone (DEX; 2 micrograms/min over 15 min every 2 h for 96 h, n = 5) or saline (n = 5). The plasma corticosteroid-binding capacity increased from 30.0 +/- 2.4 to 55.6 +/- 7.7 and 92.6 +/- 11.1 ng/ml at 48 and 96 h, respectively, of DEX infusion. To examine possible mechanisms of increasing fetal plasma CBG, we first cloned and sequenced a sheep CBG cDNA and purified the protein. This allowed us to deduce the primary structure of ovine CBG and to demonstrate that hepatic CBG mRNA abundance (single transcript of 1.8 kilobases) rose from 0.9 +/- 0.2 to 3.6 +/- 1.6 arbitrary units after 96 h of DEX treatment. Fetal DEX treatment produced a significant increase (7.1 +/- 1.2% to 13.1 +/- 1.4%) in the Concanavalin-A-binding forms of CBG that predominate in adult sheep plasma. There was negligible transfer of purified [125I]CBG from the ewe to fetal plasma, urine, or amniotic fluid. We also injected adult sheep with DEX (10 mg/day for 4 days) and demonstrated a significant decrease in plasma corticosteroid-binding capacity by 24 h, which remained suppressed for the duration of the study. After 96 h of DEX treatment, there was also a significant decrease in adult hepatic CBG mRNA abundance. We conclude that glucocorticoids increase fetal plasma CBG in part by increased hepatic biosynthesis. It may also be accentuated by a change in the glycosylation of CBG, but cannot be attributed to transplacental transfer. Furthermore, glucocorticoid treatment exerts opposite effects on CBG biosynthesis in fetal and adult sheep.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
132
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2001-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Glucocorticoid-induced increase in plasma corticosteroid-binding globulin levels in fetal sheep is associated with increased biosynthesis and alterations in glycosylation.
pubmed:affiliation
Medical Research Council Group in Fetal and Neonatal Health and Development, Lawson Research Institute, St. Joseph's Health Center, London, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't