Metabolism of testosterone to 17β-hydroxy-5α-androstane-3-one and 5α-androstane-3α, 17β-diol in alveolar macrophages from rat lung—II. Effects of intratracheal instillation of 3.4 μmol K 2Cr 2O 7

Abstract

Activity of the steroid 5α-reductase in pulmonary alveolar macrophages from adult male rats has been investigated in vitro. Intratracheal instillation of 3.4 μmol K 2Cr 2O 7 lowered the enzyme activity within 6 h, and the reduction was significant on the subsequent 2, 4 and 7 days. The activity of this enzyme was significantly decreased only 6 and 24 h after instillation when measured in the 800 g supernatant fraction of whole lung. Instillation of 3.4 μmol K 2Cr 2O 7 increased serum levels of corticosterone. Serum levels of triiodothyronine and thyroxine decreased except for a transient increase 3 h after the K 2Cr 2O 7 instillation. Subcutaneous administration of 200 μg dexamethasone/100g b.wt, 200 μg/100 gb.wt of testosterone, 17β-hydroxy-5α-androstane-3-one (5α-DHT), dehydroepiandrosterone or corticosterone had no effect on the 5α-reductase activity of the pulmonary alveolar macrophages within 12h. The combined treatment with dexamethasone s.c. and intratracheal instillation of 3.4 μmol K 2Cr 2O 7 reduced the steroid 5α-reductase activity in the pulmonary alveolar macrophages to about 25% of controls. Measurement of the steroid 5α-reductase activity in pulmonary alveolar macrophages as an index of lung damage when exposed to toxic material is discussed.