Effects in Lower Vertebrates

It is generally held that mammals possess a single AR [117] as evidenced by the complete phenotypic sex reversal displayed in humans with complete androgen insensitivity syndrome as a consequence of a single base substitution in the AR [117]. In contrast, two marine fish species, the kelp bass (Paralabrax clathratus) and Atlantic croaker (Micropogonas undulatus), have at least two ARs, termed AR1 and AR2 [118]. AR1 in the brain displays binding affinities for ligands quite distinct from AR2. AR2 from gonadal tissues of the Atlantic croaker and kelp bass has similar ligand affinities to mammalian AR. AR2 has been shown to bind p,p-DDE and vinclozolin metabolites, M1 and M2, demonstrating the ho-mology of AR function in vitro among diverse classes of vertebrates. In vivo, vinclozolin treatment induces intersex in the Medaka (Oryzias latipes), a fish species with a "mammalian type" sex differentiation process (male heteroga-metic - androgen mediated). In contrast, the fact that Makeynen et al. [119] did not obtain sex reversal in the fathead minnow with vinclozolin treatment may be related to several factors including a lack of metabolic activation of vinclo-zolin and undefined role for androgens in the sex differentiation process of this species. However, they also reported that M1 and M2 did not bind AR in the fathead minnow. The effects of vinclozolin also were studied in ovo in both birds and reptiles. Crain et al. [120] reported that in ovo treatment with vinclozolin failed to induce sex reversal in either male or female alligators, a lack of effect that is not too surprising given the key role that estrogen plays in sexual differentiation in this species. In contrast, 17b-estradiol and tamoxifen caused sex reversal from male to female, with a corresponding increase in aromatase activity. In the Japanese quail, however, male behavior was partially demasculinized by in ovo vinclozolin-treatment [121]. It is noteworthy, that in these species, as in many other vertebrates, the role of androgens in sexual differentiation is not well defined and differs from species to species.

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