Document Detail


Regulation of progesterone levels during pregnancy and parturition by signal transducer and activator of transcription 5 and 20alpha-hydroxysteroid dehydrogenase.
MedLine Citation:
PMID:  15471942     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The two highly related signal transducers and activators of transcription (Stats), Stat5a and Stat5b, are major mediators of prolactin signaling in both the mammary gland and in the ovary. Deficiencies in Stat5b, or in both Stat5a and Stat5b, result in loss of pregnancy during midgestation and are correlated with an increase in ovarian 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) and a decrease in serum progesterone, which normally declines only immediately before parturition. To determine the relative contribution of 20alpha-HSD to progesterone metabolism and Stat5 function during pregnancy and parturition, we created a 20alpha-HSD-deficient strain of mice by gene disruption. Mice deficient for 20alpha-HSD sustain high progesterone levels and display a delay in parturition of several days demonstrating that 20alpha-HSD regulates parturition downstream of the prostaglandin F2alpha receptor in an essential and nonredundant manner. Moreover, 20alpha-HSD deficiency partially corrected the abortion of pregnancies associated with Stat5b deficiency, supporting the concept that prolactin activation of Stat5b is important in suppressing 20alpha-HSD gene expression and thereby allowing the maintenance of progesterone levels that are required to sustain pregnancy.
Authors:
Roland P Piekorz; Sébastien Gingras; Angelika Hoffmeyer; James N Ihle; Yacob Weinstein
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2004-10-07
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  19     ISSN:  0888-8809     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-01-26     Completed Date:  2005-06-07     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  431-40     Citation Subset:  IM    
Affiliation:
Howard Hughes Medical Institute, Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
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MeSH Terms
Descriptor/Qualifier:
20-alpha-Hydroxysteroid Dehydrogenase / metabolism*
Adrenal Glands / metabolism
Animals
Blotting, Northern
Blotting, Western
Cloprostenol / pharmacology
DNA-Binding Proteins / metabolism*
Dose-Response Relationship, Drug
Down-Regulation
Electrophoresis, Polyacrylamide Gel
Female
Genetic Vectors
Genotype
Hematopoiesis
Hematopoietic Stem Cells / cytology
Kidney / metabolism
Mammary Glands, Animal / metabolism
Mice
Mifepristone / pharmacology
Milk Proteins / metabolism*
Models, Genetic
Mutation
Ovary / metabolism
Parturition
Pregnancy
Pregnancy, Animal*
Progesterone / biosynthesis*,  blood,  metabolism
Radioimmunoassay
Receptors, Prostaglandin / metabolism
STAT5 Transcription Factor
Time Factors
Trans-Activators / metabolism*
Grant Support
ID/Acronym/Agency:
CA21765/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Milk Proteins; 0/Receptors, Prostaglandin; 0/STAT5 Transcription Factor; 0/Stat5a protein, mouse; 0/Stat5b protein, mouse; 0/Trans-Activators; 0/prostaglandin F2alpha receptor; 40665-92-7/Cloprostenol; 57-83-0/Progesterone; 84371-65-3/Mifepristone; EC 1.1.1.149/20-alpha-Hydroxysteroid Dehydrogenase

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


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