Other
12 Authors
- Chen H,
- Wolf IM,
- Chen Z,
- Yang Z,
- Shou W,
- Periyasamy S,
- Zhao W,
- Xu J,
- Sánchez ER,
- Yong W,
- Shi S,
- Srivastava A
| First Author | Yang Z | Year | 2006 |
| Journal | Mol Endocrinol | Volume | 20 |
| Issue | 11 | Pages | 2682-94 |
| PubMed ID | 16873445 | Mgi Jnum | J:114715 |
| Mgi Id | MGI:3689785 | Doi | 10.1210/me.2006-0024 |
| Citation | Yang Z, et al. (2006) FK506-binding protein 52 is essential to uterine reproductive physiology controlled by the progesterone receptor a isoform. Mol Endocrinol 20(11):2682-94 |
| abstractText | FK506-binding protein 52 (FKBP52) is a tetratricopeptide repeat protein that associates with steroid receptors in complexes containing heat shock protein 90. To investigate the role of FKBP52 in steroid-regulated physiology, we generated FKBP52-deficient mice. FKBP52 (-/-) females are sterile due to a complete failure of implantation, a process that requires estrogen (ER) and progesterone receptors (PR). Because the uterus expresses two forms of PR, PR-A and PR-B, we investigated all three receptors as potential targets of FKBP52 action. FKBP52 (-/-) uteri showed a normal growth response to estradiol, and unaltered expression of genes controlled by ER and PR-B. In contrast, FKBP52 (-/-) uteri were neither able to express two PR-A-regulated genes, nor undergo decidualization in response to progesterone, suggesting that FKBP52 specifically regulates PR-A at this organ. Analysis of uterine PR heterocomplexes showed preferential association of FKBP52 with PR-A compared with PR-B. Loss of FKBP52 neither disrupted the PR-A/heat shock protein 90 interaction, nor impaired uterine PR-A hormone-binding function, demonstrating the essential role of FKBP52 in PR-A action to be downstream of the hormone-binding event. Transcription studies in +/+ and -/- mouse embryonic fibroblast cells showed a near-complete loss of PR-A activity at mouse mammary tumor virus and synthetic progesterone response element promoters, although partial reductions of ER and PR-B were also observed. Partial disruptions of ovulation and mammary development were also found in FKBP52 (-/-) females. Taken as a whole, our results show FKBP52 to be an essential regulator of PR-A action in the uterus, while being a nonessential but contributory regulator of steroid receptors in the mammary and ovary. These data may now provide the basis for selective targeting of steroid-regulated physiology through tetratricopeptide repeat proteins. |
