title: Developmental toxicity of testosterone in the crustacean Daphnia magna involves anti-ecdysteroidal activity.
abstract: Testosterone has been shown to cause developmental arrest of embryonic daphnids (Daphnia magna). The present study was undertaken to determine whether this toxicity might be due to anti-ecdysteroidal activity associated with testosterone. The effect of testosterone on molt frequency of early instar daphnids was first evaluated to determine whether testosterone interfered with this ecdysteroid-regulated process. Molt frequency was delayed by exposure to testosterone and this effect was mitigated by co-exposure to the ecdysteroid 20-hydroxyecdysone. Testosterone exposure concentrations that interfered with molting also elicited developmental abnormalities among neonatal organisms produced by maternal organisms that were continuously exposed to testosterone or among embryos that were removed from unexposed mothers and exposed directly to the hormone. Embryos were significantly protected against the developmental toxicity of testosterone by co-exposure to 20-hydroxyecdysone. Taken together, these results demonstrated that the embryo toxicity of testosterone to daphnids is due largely to its ability to interfere with ecdysteroid control of development. Experiments next were conducted to determine whether testosterone interfered with ecdysteroidal activity by acting as an ecdysone receptor antagonist or by reducing endogenous ecdysone levels. Testosterone significantly antagonized the action of 20-hydroxyecdysone in an ecdysone-responsive cell line. Testosterone had no discernable effect on endogenous ecdysone levels in daphnids. These results demonstrated that (1). ecdysteroids regulate critical processes in daphnid embryo development, (2). testosterone elicits embryo toxicity to daphnids by interfering with ecdysteroid activity, and (3). ecdysteroid receptor antagonism could be one mechanism by which testosterone elicits these effects.
authors.affiliation: Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, NC 27695-7633 USA.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Mu
authors.forename: Gerald A
authors.initials: GA
authors.lastname: LeBlanc
mesh_terms: D000818:Animals; D003445:Crustacea / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development*; D026461:Ecdysteroids / Q000037:antagonists & inhibitors*; D004441:Ecdysterone / Q000494:pharmacology; D004625:Embryo, Nonmammalian / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000506:poisoning*; D018978:Molting / Q000187:drug effects; D013739:Testosterone / Q000506:poisoning*
chemical_list: D026461:Ecdysteroids; D012739:Gonadal Steroid Hormones; D013739:Testosterone; D004441:Ecdysterone