Abstract:
:Progesterone (P(4)) signaling is critical for pregnancy. We previously showed that immunopilin FK506 binding protein (FKBP)52 serves as a cochaperone to optimize progesterone receptor (PR) function in the uterus, and its deficiency leads to P(4) resistance in a pregnancy stage-specific and genetic background-dependent manner in mice. In particular, sc placement of SILASTIC implants carrying P(4) rescued implantation failure in CD1 Fkbp52(-/-) mice, but the resorption rate was substantially high at midgestation due to reduced P(4) responsiveness. Because downstream targets of P(4)-FKBP52-PR signaling in the uterus to support pregnancy are not clearly understood, we performed proteomic analysis using Fkbp52(-/-), PR-deficient (Pgr(-/-)), and wild-type (WT) uteri. We found that the expression of galectin-1 (Gal1), an evolutionarily conserved glycan-binding protein, was significantly down-regulated in both Fkbp52(-/-) and Pgr(-/-) uteri compared with WT uteri. During early gestation, Lgals1, which encodes Gal1, was distinctly expressed in stromal and decidual cells. Lgals1 expression was much lower in d 4 Fkbp52(-/-) uteri compared with WT uteri, and this reduction was reversed by P(4) supplementation. More interestingly, concomitant supplementation of recombinant Gal1 significantly suppressed the high resorption rate and leukocyte infiltration at implantation sites in CD1 Fkbp52(-/-) females carrying P(4) SILASTIC implants. These findings suggest that uterine Gal1 is an important downstream target of P(4)-FKBP52-PR signaling in the uterus to support P(4) responsiveness during pregnancy.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Hirota Y,Burnum KE,Acar N,Rabinovich GA,Daikoku T,Dey SKdoi
10.1210/en.2012-1035subject
Has Abstractpub_date
2012-05-01 00:00:00pages
2486-93issue
5eissn
0013-7227issn
1945-7170pii
en.2012-1035journal_volume
153pub_type
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