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

• 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 (GR). 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

Animals

Blotting

Western/methods

Dexamethasone/metabolism/pharmacology

Estrenes/pharmacology

Female

Furans/pharmacology

Gene Expression Regulation

Developmental

Glucocorticoids/metabolism/pharmacology

Immunohistochemistry/methods

Immunoprecipitation/methods

Lung/chemistry/growth & development/*metabolism

Mice

Mice

Inbred C57BL

Microscopy

Confocal

Mifepristone/pharmacology

Progesterone/antagonists & inhibitors/metabolism/pharmacology

Protein Isoforms/analysis/*metabolism

RNA

Messenger/analysis

Receptors

Glucocorticoid/*metabolism

Receptors

Progesterone/antagonists & inhibitors/genetics/*metabolism

Reverse Transcriptase Polymerase Chain Reaction

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)