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Developmental and hormonal regulation of progesterone receptor A-form expression in female mouse lung in vivo: interaction with glucocorticoid receptors

Shao, Ruijin ; Egecioglu, Emil ; Weijdegard, Birgitta ; Ljungstrom, Karin ; Ling, Charlotte LU ; Fernandez-Rodriguez, Julia and Billig, Hakan (2006) In Journal of Endocrinology 190(3). p.857-870
Abstract
Progesterone (P-4) regulates many aspects of physiological functions via two nuclear P-4 receptors (PR), PRA and PRB, which are members of a structurally related nuclear hormone receptor superfamily that includes glucocorticoid receptors (Gk). The regulation and cellular distribution of PR protein isoforms have been extensively studied in reproductive tissues, but this is not the case in the lung. In the present study, reverse transcriptase (RT)-PCR, Western blotting, and immunolocalization supported the presence of PRA in the lung of female mice, with PRA protein levels significantly increased between postnatal day 7 and 12, declined at postnatal day 26, and minimal in adults when compared to postnatal day 2. The peak was temporally... (More)
Progesterone (P-4) regulates many aspects of physiological functions via two nuclear P-4 receptors (PR), PRA and PRB, which are members of a structurally related nuclear hormone receptor superfamily that includes glucocorticoid receptors (Gk). The regulation and cellular distribution of PR protein isoforms have been extensively studied in reproductive tissues, but this is not the case in the lung. In the present study, reverse transcriptase (RT)-PCR, Western blotting, and immunolocalization supported the presence of PRA in the lung of female mice, with PRA protein levels significantly increased between postnatal day 7 and 12, declined at postnatal day 26, and minimal in adults when compared to postnatal day 2. The peak was temporally related to postnatal lung maturation in rodents. Immunoreactivity for PR was detected in the alveolar and bronchial epithelia. We then extended this study to examine, for the first time, the regulation of PRA protein expression in female mouse lung in vivo. Neither the increase in endogenous P-4 nor treatment with exogenous P-4 regulated PRA protein expression in female mouse lung. However, treatment of mice with the GR/PR antagonist RU 486, but not Org 31710 (a specific PR antagonist), significantly increased PRA protein expression in parallel to a decrease in GR protein expression. In addition, treatment with the synthetic glucocorticoid dexamethasone led to a decrease in PRA protein expression independent of endogenous P-4 levels. Furthermore, immunoprecipitation followed by Western blot analysis revealed that, under in vivo conditions, PRA physically interacted with GR in mouse lung. Confocal laser microscopy revealed that PRA and GR co-localized in the nuclei of alveolar epithelia cells, whereas nuclear PR and cytoplasmic GR were detected in bronchial epithelium. Taken together, our observations suggest that PRA may be an important physiological factor involved in postnatal lung development and that the regulation of PRA protein expression is not dependent on P-4, but rather on functional glucocorticoid/GR signaling mediated by protein-protein interaction in the mouse lung. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Endocrinology
volume
190
issue
3
pages
857 - 870
publisher
Society for Endocrinology
external identifiers
  • wos:000241324000030
  • scopus:33749866926
ISSN
1479-6805
DOI
10.1677/joe.1.06896
language
English
LU publication?
yes
id
7590907d-97db-40be-8f18-4bc74955726f (old id 387958)
alternative location
http://joe.endocrinology-journals.org/cgi/content/abstract/190/3/857
date added to LUP
2016-04-01 11:42:39
date last changed
2020-09-30 02:02:55
@article{7590907d-97db-40be-8f18-4bc74955726f,
  abstract     = {Progesterone (P-4) regulates many aspects of physiological functions via two nuclear P-4 receptors (PR), PRA and PRB, which are members of a structurally related nuclear hormone receptor superfamily that includes glucocorticoid receptors (Gk). The regulation and cellular distribution of PR protein isoforms have been extensively studied in reproductive tissues, but this is not the case in the lung. In the present study, reverse transcriptase (RT)-PCR, Western blotting, and immunolocalization supported the presence of PRA in the lung of female mice, with PRA protein levels significantly increased between postnatal day 7 and 12, declined at postnatal day 26, and minimal in adults when compared to postnatal day 2. The peak was temporally related to postnatal lung maturation in rodents. Immunoreactivity for PR was detected in the alveolar and bronchial epithelia. We then extended this study to examine, for the first time, the regulation of PRA protein expression in female mouse lung in vivo. Neither the increase in endogenous P-4 nor treatment with exogenous P-4 regulated PRA protein expression in female mouse lung. However, treatment of mice with the GR/PR antagonist RU 486, but not Org 31710 (a specific PR antagonist), significantly increased PRA protein expression in parallel to a decrease in GR protein expression. In addition, treatment with the synthetic glucocorticoid dexamethasone led to a decrease in PRA protein expression independent of endogenous P-4 levels. Furthermore, immunoprecipitation followed by Western blot analysis revealed that, under in vivo conditions, PRA physically interacted with GR in mouse lung. Confocal laser microscopy revealed that PRA and GR co-localized in the nuclei of alveolar epithelia cells, whereas nuclear PR and cytoplasmic GR were detected in bronchial epithelium. Taken together, our observations suggest that PRA may be an important physiological factor involved in postnatal lung development and that the regulation of PRA protein expression is not dependent on P-4, but rather on functional glucocorticoid/GR signaling mediated by protein-protein interaction in the mouse lung.},
  author       = {Shao, Ruijin and Egecioglu, Emil and Weijdegard, Birgitta and Ljungstrom, Karin and Ling, Charlotte and Fernandez-Rodriguez, Julia and Billig, Hakan},
  issn         = {1479-6805},
  language     = {eng},
  number       = {3},
  pages        = {857--870},
  publisher    = {Society for Endocrinology},
  series       = {Journal of Endocrinology},
  title        = {Developmental and hormonal regulation of progesterone receptor A-form expression in female mouse lung in vivo: interaction with glucocorticoid receptors},
  url          = {http://dx.doi.org/10.1677/joe.1.06896},
  doi          = {10.1677/joe.1.06896},
  volume       = {190},
  year         = {2006},
}