COMPARATIVE ABILITY OF SOME STEROIDS AND THEIR ESTERS TO ENHANCE THE RENAL β-GLUCURONIDASE ACTIVITY OF MICE

Abstract

Listen

Translate article

In earlier studies from this laboratory (l-3), it was demonstrated that on parenteral administration certain steroids, particularly those closely related to testosterone, possessed the ability to enhance the kidney /3-glucuronidase activity of various strains of mice. Fishman, Artenstein, and Green (3) established experimental conditions which made it possible to obtain uniform and reproducible figures for mouse kidney &glucuronidase activity in the Ajax strain of mice. A large number of steroids were screened. Androgens as a group were found to increase renal p-glucuronidase, seven out of forty-nine pregnane and corticoid derivatives showed weak activity, and estrogens and progesterone were without effect. With use of testosterone as the reference steroid (which gave a 3-fold response), they found that the following changes in the molecule enhanced the potency: (1) esterification of the 17p-OH, (2) introduction of a 17~CHo group, (3) reduction of the A4 double bond, and (4) elimination of the 19-CH3 group. The following alterations reduced potency: replacement of the 17@OH (1) by a 17~0H, (2) by a 17-ketone, and (3) by introduction of an lla-, 14cr-, or 6/3-OH group. In the AK-androstenediol series, enhancement of activity was seen in the 17a-CH3 compound, the potency of which was reduced by blocking the 17P-OH group or by oxidizing it to a 17-keto group. In the present report, conditions are described which make the assay more reliable and significant for steroids highly potent with regard to the renal &glucuronidase response. By this means, it was discovered that esters of testosterone had a much higher order of activity than that shown by unesterified testosterone. Moreover, the study of newer compounds by the “screening” method has yielded findings which bear on the relationship between structure and activity of some protein-anabolic steroids.