Non-specific steroidal esterase activity and distribution in human and other mammalian tissues

Abstract

An NADPH dependent arylamine carcinogen and fatty acid steroid ester metabolizing esterase activity belonging to the B- or carboxylesterase class of non-specific esterase (EC 3.1.1.1) was measured by two different methods: (i) a spectrophotometric assay using alpha naphthyl acetate (ANA) as substrate and (ii) a radiometric method using the conversion of beclomethasone-17,21-dipropionate to beclomethasone-17-monopropionate as the endpoint. The two methods were strongly correlated when assayed in human mononuclear leukocytes ( r = 0.89, P < 0.0001) and human mammary tissue ( r = 0.91, P < 0.0001). Hence it was concluded that the two substrates are metabolized at least in part by the same enzyme. This esterase activity was abundant in human monocytes, present in T-lymphocytes and equally divided between CD4 and CD8 T-Iymphocyte subsets. The same activity was expressed in human liver, colon, stomach, breast and brain tissues. The distribution of this esterase in human tissues showed high activity in liver, intermediate activity in colon, stomach and breast and low activity in brain tissue. The interorgan distribution observed in human tissues was closely mimicked when the esterase activity was assessed in liver, colon and brain tissues from three mouse strains and three rat strains. The non-specific steroidal esterase activity determined by ANA metabolism in human mammary tissue was shown to be reproducible when assayed as triplicate samples from each of 16 different women (intraclass correlation coefficient 67.3%, P < 0.03). The interindividual variation in mammary tissue was high (18.4-fold) and there was a positive correlation between the esterase activity and age ( r = 0.58, P < 0.01), as well as a tendency toward bimodal distribution. To our knowledge, these data represent the first systematic study of interorgan and interspecies comparisons of a non-specific steroidal esterase activity.