Effects of the glucocorticoid agonist, RU28362, and the antagonist RU486 on lung phosphatidylcholine and antioxidant enzyme development in the genetically obese Zucker rat.
The biochemical maturation of the lung in late gestation and in the young animal is regulated by glucocorticoids. The present study was aimed at dissociating the different glucocorticoid receptor sites involved in these regulatory functions. The obese Zucker rat was selected as a model for this study as it exhibits hypersensitivity to glucocorticoid hormone action by virtue of its elevated receptor numbers and activity. Two synthetic steroid analogues were administered to obese animals; RU28362, a specific type II receptor agonist, and the type II antagonist RU486. RU28362 promoted a strong catabolic effect, which was associated with reduced food intake and the abolition of growth in the rats. The agonist, RU28362, attenuated developmental increases in antioxidant enzyme activities, and altered the growth of the tissue. At the age studied, development of the lung phosphatidylcholine (PC) system was almost complete, but RU28362 increased disaturated PC 16:0/16:0 concentrations by almost 2-fold, and altered the molecular composition of total pulmonary PC. RU486 attenuated the growth of the rats and reduced their food intake. Treatment with the type II antagonist attenuated lung growth and increased the activities of pulmonary copper zinc (Cu/Zn) and manganese (Mn) superoxide dismutases. RU486 had no effect on lung PC concentrations and molecular composition. The data suggest a role for type I glucocorticoid receptors in the regulation of the antioxidant enzyme system in the lung, as type II antagonism will channel endogenous glucocorticoid binding to the type I site. Type II receptor binding would appear to play a role in regulating the lung PC content.
Langley
S C
SC
Department of Human Nutrition, University of Southampton, U.K.
Rickett
G W
GW
Hunt
A
A
Kelly
F J
FJ
Postle
A D
AD
York
D A
DA
D000732:Androstanols / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005938:Glucocorticoids / Q000037:antagonists & inhibitors; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D015735:Mifepristone / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000187:drug effects*
D000732:Androstanols; D005938:Glucocorticoids; D010743:Phospholipids; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one