Gonadectomy and progesterone treatment induce protection in murine cysticercosis.
The effects of progesterone on castrated mice of both sexes infected with Taenia crassiceps cysticerci were studied. Gonadectomy and treatment with progesterone before infection decreased parasite loads by 100% compared with intact uninfected mice. mRNA levels of IFN-gamma and IL-2 (typically associated to Th1-like profiles) were markedly decreased in infected gonadectomized (Gx) mice, whereas progesterone treatment of infected Gx mice did not affected its expression. mRNA levels of IL-4, and IL-10 (typically associated with Th2-like profiles) were reduced by gonadectomy, whereas restitution with progesterone did not affected this pattern in infected Gx progesterone-treated mice. Infection markedly induced expression of progesterone receptor isoform A in splenocytes of Gx mice (5-fold), whereas isoform B had no changes. Progesterone metabolism to dehydroepiandrosterone (DHEA) in Gx animals was increased 3-fold only in infected progesterone-treated uninfecteds of both sexes, but was not detectable in infected Gx progesterone-treated mice. Conversely, DHEA levels increased 100-fold in infected Gx progesterone-treated mice. However, androgen receptor expression in splenocytes of male mice showed a reduction by gonadectomy, and by infection, whereas in females AR expression showed no changes in the different mouse groups. These results suggest that progesterone, through its metabolism to DHEA, negatively affects the establishment, growth, and reproduction of Taenia crassiceps, by a mechanism that does not implicate a classic genomic pathway involving a nuclear androgen receptor.
Vargas-Villavicencio
J A
JA
Departamento de Inmunología, Instituto de Investigaciones Biomédicas, UNAM, México DF, México.
Larralde
C
C
Morales-Montor
J
J
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D003551:Cysticercosis / Q000276:immunology* / Q000469:parasitology; D003552:Cysticercus / Q000187:drug effects; D003687:Dehydroepiandrosterone / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009919:Orchiectomy; D010052:Ovariectomy; D011374:Progesterone / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D011372:Progestins / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D013621:Taenia / Q000187:drug effects / Q000254:growth & development; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D011372:Progestins; D003687:Dehydroepiandrosterone; D011374:Progesterone