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, cont aining a highly labile hydoxyphenyl aziridine or precursor, and a more stab le analog, compound A inhibits sheep adrenal cytochrome P450c11. In additio n, 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 th ese compounds. The present study was undertaken to establish which mechanis m would predominate in female rats. Compound A significantly (P < 0.01) dis placed glucocorticoids, but not progesterone, from rat CBG in vitro, wherea s in vitro the percentage of free plasma corticosterone in both S, tubercul atiformis (P < 0.05)- and compound A (P < 0.01)-treated rats was also signi ficantly higher due to displacement from CBG. In addition, both ACTH and CB G concentrations were significantly (P < 0.05) lower than control values. T he 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 displace ment of endogenous corticosterone could be part of the contraceptive mechan ism of S. tuberculatiformis and the aziridine precursor, compound A.