Wpm. Benten et al., TESTOSTERONE-INDUCED SUSCEPTIBILITY TO PLASMODIUM-CHABAUDI MALARIA - PERSISTENCE AFTER WITHDRAWAL OF TESTOSTERONE, Journal of Endocrinology, 153(2), 1997, pp. 275-281
Testosterone induces susceptibility to Plasmodium chabaudi malaria by
imposing restrictions on those mechanisms which mediate resistance con
trolled by genes of the H-2 complex and the non-H-2 background in mice
. This study investigated whether these restrictions are abolished aft
er withdrawal of testosterone. Female mice of the inbred strain C57BL/
10 were treated with 0.9 mg testosterone twice a week for 3 weeks and
testosterone was then withdrawn for 12 weeks. The treatment raised pla
sma testosterone levels from 0.18 ng/ml to 3.79 ng/ml. After the testo
sterone treatment, these levels progressively dropped and reached 0.21
ng/ml by week 12 after testosterone withdrawal. Surprisingly, however
, the testosterone-induced susceptibility still persisted. When mice w
ere challenged on week 12 after testosterone withdrawal, P. chabaudi i
nfections were still fatal in testosterone-treated mice, in contrast t
o self-healing infections in resistant, i.e. untreated, control mice.
In addition, testosterone caused a persistent decrease in the levels o
f total IgG antibodies, especially IgG1 and IgG2b isotypes. In contras
t, testosterone-induced changes in spleen cells, such as the reduction
in number by 50%, the relative increase in CD8(+) cells and the decre
ase in Ig(+) cells, as well as the acquisition of the susceptible phen
otype, were completely reversed on week 10 after testosterone withdraw
al at the latest. Testosterone did not affect the production of the T(
H)1-signalling cytokine interferon-gamma and the T(H)2-signalling cyto
kines interleukin (IL)-4 and IL-10 in response to P. chabaudi malaria.
Together, our data indicated that the gene-controlled host resistance
to P. chabaudi malaria is subject to superior hormonal imprinting: wh
en once induced by testosterone, mechanisms which suppress resistance
thus causing susceptibility persist independently of testosterone.