Abstract:
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 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.
