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This version published online on October 7, 2004
Molecular Endocrinology, doi:10.1210/me.2004-0302
A more recent version of this article appeared on February 1, 2005
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Submitted on July 27, 2004
Accepted on September 27, 2004

Regulation of Progesterone Levels during Pregnancy and Parturition by Stat5 and 20{alpha}-Hydroxysteroid Dehydrogenase

Roland P. Piekorz, Sébastien Gingras, Angelika Hoffmeyer, James N. Ihle*, and Yacob Weinstein

Howard Hughes Medical Institute, Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN38105; Faculty of Health Sciences, Department of Microbiology and Immunology, Ben Gurion University of the Negev, Beer Sheva, Israel 84105

* To whom correspondence should be addressed. E-mail: james.ihle{at}stjude.org.

The two highly related signal transducers and activators of transcription (Stat) 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 mid-gestation and are correlated with an increase in ovarian 20{alpha}-HSD and a decrease in serum progesterone, which normally only declines immediately before parturition. To determine the relative contribution of 20{alpha}-HSD to progesterone metabolism and Stat5 function during pregnancy and parturition we created a 20{alpha}-HSD deficient strain of mice by gene disruption. Mice deficient for 20{alpha}-HSD sustain high progesterone levels and display a delay in parturition of several days demonstrating that 20{alpha}-HSD regulates parturition downstream of the prostaglandin F2{alpha} (PGF2{alpha}) receptor in an essential and non-redundant manner. Moreover, 20{alpha}-HSD deficiency partially corrected the abortion of pregnancies associated with Stat5b deficiency supporting the concept that prolactin activation of Stat5b is important in suppressing 20{alpha}-HSD gene expression and thereby allowing the maintenance of progesterone levels that are required to sustain pregnancy.
Key words: Stat5 • 20{alpha}-hydroxysteriod dehydrogenase • prolactin • progesterone • pregnancy • Subject Categories: Development • Signal Transduction

NURSA Molecule Pages Link:

Ligands:   Progesterone



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