title: Steroid synthesis by Taenia crassiceps WFU cysticerci is regulated by enzyme inhibitors.
abstract: Cysticerci and tapeworms from Taenia crassiceps WFU, ORF and Taenia solium synthesize sex-steroid hormones in vitro. Corticosteroids increase the 17β-estradiol synthesis by T. crassiceps cysticerci. T. crassiceps WFU cysticerci synthesize corticosteroids, mainly 11-deoxycorticosterone (DOC). The aim of this work was to investigate whether classical steroidogenic inhibitors modify the capacity of T. crassiceps WFU cysticerci to synthesize corticosteroids and sex steroid hormones. For this purpose, T. crassiceps WFU cysticerci were obtained from the abdominal cavity of mice, pre-cultured for 24h in DMEM+antibiotics/antimycotics and cultured in the presence of tritiated progesterone ((3)H-P4), androstendione ((3)H-A4), or dehydroepiandrosterone ((3)H-DHEA) plus different doses of the corresponding inhibitors, for different periods. Blanks with the culture media adding the tritiated precursors were simultaneously incubated. At the end of the incubation period, parasites were separated and media extracted with ether. The resulting steroids were separated by thin layer chromatography (TLC). Data were expressed as percent transformation of the tritiated precursors. Results showed that after 2h of exposure of the cysticerci to 100 μM formestane, the (3)H-17β-estradiol synthesis from tritiated androstenedione was significantly inhibited. The incubation of cysticerci in the presence of (3)H-DHEA and danazol (100 nM) resulted in (3)H-androstenediol accumulation and a significant reduction of the 17β-estradiol synthesis. The cysticerci (3)H-DOC synthesis was significantly inhibited when the parasites were cultured in the presence of different ketoconazole dosis. The drug treatments did not affect parasite's viability. The results of this study showed that corticosteroid and sex steroid synthesis in T. crassiceps WFU cysticerci can be modified by steroidogenic enzyme inhibitors. As was shown previously by our laboratory and others, parasite survival and development depends on sex steroids, therefore the inhibition of their synthesis is a good starting point exploited in situations where the inhibition of steroidogenesis could help to control the infection for the development of new treatments, or replacement of the usual therapy in resistant parasite infections. We raise the possibility that these drug actions may be beneficially.
authors.affiliation: Dpto. de Fisiología, Biofísica y Neurociencias, CINVESTAV del I.P.N., Apdo. Postal 14-740, 07360 Mexico D.F., Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Aceves-Ramos
authors.forename: R A
authors.initials: RA
authors.lastname: Valdez
authors.forename: B
authors.initials: B
authors.lastname: Gaona
authors.forename: K
authors.initials: K
authors.lastname: Willms
authors.forename: M C
authors.initials: MC
authors.lastname: Romano
mesh_terms: D000735:Androstenedione / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002855:Chromatography, Thin Layer; D003613:Danazol / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004958:Estradiol / Q000378:metabolism; D007654:Ketoconazole / Q000494:pharmacology; D013256:Steroids / Q000378:metabolism*; D013621:Taenia / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D013256:Steroids; D000735:Androstenedione; D003900:Desoxycorticosterone; D004958:Estradiol; D003613:Danazol; C014594:formestane; D007654:Ketoconazole