As indicated above, the effects of PZ on sexual differentiation of androgen-dependent tissues could result from dual modes of action. PZ act as an AR antagonist and it inhibits testosterone production in the fetal testis. Ex vivo testosterone production is significantly reduced in testes at GD 18 from male fetuses exposed in utero from GD 14 to GD 18, whereas progesterone and hydroxyprogester-one production are increased by as much as 10-fold. Together, the results presented by Wilson et al. and the current study indicate that PZ effects on fetal testes differed from effects of antiandrogens linuron and diethylhexyl phthalate, which decreased testicular testosterone production and left levels of progesterone unaffected.
PZ-induced alterations in the steroidal milieu are consistent with the observation that 17,20 lyase may be among the most sensitive of the P450-dependent steroidogenic enzymes inhibited by some imidazoles.
While the developmental effects of PZ on weights of androgen-sensitive tissues in male offspring could result either from AR antagonism or from reduced testosterone synthesis, the profile of male reproductive tract malformations induced by PZ appears similar to effects observed with other classes of antiandrogens that are AR antagonists, such as flutamide or vinclozolin but differs from profiles of the phthalate esters that inhibit fetal testosterone synthesis but do not bind AR.