Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 in Alveolar Epithelial Cells in Rats

摘要

11β-Hydroxy steroid dehydrogenase type 1 (11β-HSD1) behaves predominantly as an oxoreductase converting the receptor-inactive glucocorticoids to their active forms in vivo, while the type 2 isoform (11β-HSD2) possesses only dehydrogenase activity and inactivates cortisol in human or corticosterone in rat. We determined enzyme activity of 11β-HSD in rat lungs from fetus to adult, and examined whether 11β-HSD1 exists in alveolar type Ⅱ cells, the most important site for the synthesis of pulmonary surfactant in mature lungs, by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Enzyme activity of 11β-HSD1 and 2 in lung tissue homogenate were determined as NADP~+- and NAD~+-dependent conversion of corticosterone to 11-dehydrocorticosterone, respectively. We found that 11β-HSD1 activity was increased progressively from 21 days gestation to 7 weeks after birth. 11β-HSD2 activity was significantly lower than that of 11β-HSD1 throughout gestation and after birth. Immunoreactivity for 11β-HSD1 was detected in the cytoplasm of the cells in the alveolar region of adult rats. Some of these expressing 11β-HSD1 were considered to be alveolar type Ⅱ cells, because of their cuboid shape and localization at the corner of the alveoli. RT-PCR demonstrated 11β-HSD1 mRNA in isolated alveolar type Ⅱ cells. Our results suggest that alveolar type Ⅱ cells enhance intracellular glucocorticoid availability via 11β-HSD1. 11β-HSD1 in alveolar type Ⅱ cells is thought of as an autocrine amplifier of glucocorticoid action in the lung.