Salsola Tuberculatiformis Botschantzev and an Aziridine Precursor Analog Mediate the in Vivo Increase in Free Corticosterone and Decrease in Corticosteroid-binding Globulin in Female Wistar Rats

Salsola tuberculatiformis Botschantzev causes prolonged gestation in sheep and contraception in rats. An active fraction isolated from the shrub, containing a highly labile hydoxyphenyl aziridine or precursor, and a more stable analog, compound A, inhibits sheep adrenal cytochrome P450c11. In addition, compound A has been shown to bind to and be stabilized by corticosteroid-binding globulin (CBG). Binding may result in concomitant displacement of endogenous steroids, which could contribute to the biological effects of these compounds. The present study was undertaken to establish which mechanism would predominate in female rats. Compound A significantly (P < 0.01) displaced glucocorticoids, but not progesterone, from rat CBG in vitro, whereas in vivo the percentage of free plasma corticosterone in both S. tuberculatiformis (P < 0.05)- and compound A (P < 0.01)-treated rats was also significantly higher due to displacement from CBG. In addition, both ACTH and CBG concentrations were significantly (P < 0.05) lower than control values. The levels of the gonadotropins were also reduced during treatment, but only LH values significantly (P < 0.05) so. These results suggest that binding of the test substances to CBG in female rat plasma and concomitant displacement of endogenous corticosterone could be part of the contraceptive mechanism of S. tuberculatiformis and the aziridine precursor, compound A.