Expression of 11 beta-hydroxysteroid dehydrogenase type 1 in alveolar epithelial cells in rats.
11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) behaves predominantly as an oxoreductase converting the receptor-inactive glucocorticoids to their active forms in vivo, while the type 2 isoform (11beta-HSD2) possesses only dehydrogenase activity and inactivates cortisol in human or corticosterone in rat. We determined enzyme activity of 11beta-HSD in rat lungs from fetus to adult, and examined whether 11beta-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 11beta-HSD1 and 2 in lung tissue homogenate were determined as NADP(+)- and NAD(+)-dependent conversion of corticosterone to 11-dehydrocorticosterone, respectively. We found that 11beta-HSD1 activity was increased progressively from 21 days gestation to 7 weeks after birth. 11beta-HSD2 activity was significantly lower than that of 11beta-HSD1 throughout gestation and after birth. Immunoreactivity for 11beta-HSD1 was detected in the cytoplasm of the cells in the alveolar region of adult rats. Some of these expressing 11beta-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 11beta-HSD1 mRNA in isolated alveolar type II cells. Our results suggest that alveolar type II cells enhance intracellular glucocorticoid availability via 11beta-HSD1. 11beta-HSD1 in alveolar type II cells is thought of as an autocrine amplifier of glucocorticoid action in the lung.
Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Satoshi
S
Suzuki
Hiroyoshi
H
Tsubochi
Andrew
A
Darnel
Takashi
T
Suzuki
Hironobu
H
Sasano
Zigmunt S
ZS
Krozowski
Takashi
T
Kondo
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism*; D000375:Aging / Q000378:metabolism; D000818:Animals; D004847:Epithelial Cells / Q000201:enzymology; D005333:Fetus / Q000378:metabolism; D005865:Gestational Age; D007150:Immunohistochemistry; D011650:Pulmonary Alveoli / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1