Functional specific binding of testosterone to Schistosoma haematobium 28-kilodalton glutathione S-transferase.
During parasitic disease such as schistosomiasis, sex hormones have an important influence on the age- and gender-dependent level of infection. Since mammal glutathione S-transferase (GST) has the ability to bind hormones and particularly sexual steroids to influence their transport, metabolism, and physiological action, we have evaluated the capacity of testosterone to bind the 28-kDa GST of the Schistosoma haematobium parasite (Sh28GST). For the first time, we have demonstrated a specific binding of testosterone to parasite GST protein with high affinity (K(d) = 2.57 x 10(-7) M). In addition, we have assessed the effect of this binding on Sh28GST enzymatic activity, a mechanism closely associated with the reduction of Schistosoma fecundity. We showed that testosterone has the functional ability to inhibit the Sh28GST enzymatic activity in a dose-dependent manner, suggesting that this hormone could be directly involved in an antifecundity mechanism. This effect seemed to be related to the binding of testosterone to one peptide involved in the enzymatic site (i.e., amino acids 24 to 43). During human infection, binding of sexual hormones to Schistosoma Sh28GST could play a key role in parasite metabolism, especially the decrease of fecundity, and could be involved in the sex-dependent immune response to Sh28GST that we have previously observed in infected adults.
Remoué
Franck
F
Unité INSERM U547, Institut Pasteur de Lille, Lille. Faculté de Pharmacie, Unité CNRS UMR 9921, Montpellier, France. franck.remoue@ulg.ac.be
Mani
Jean-Claude
JC
Pugnière
Martine
M
Schacht
Anne-Marie
AM
Capron
André
A
Riveau
Gilles
G
D000818:Animals; D000947:Antigens, Helminth / Q000378:metabolism*; D001665:Binding Sites; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015801:Helminth Proteins; D010455:Peptides / Q000037:antagonists & inhibitors / Q000737:chemistry; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D012548:Schistosoma haematobium / Q000201:enzymology* / Q000378:metabolism; D012553:Schistosomiasis haematobia / Q000378:metabolism; D013739:Testosterone / Q000031:analogs & derivatives* / Q000378:metabolism*
D000947:Antigens, Helminth; D015801:Helminth Proteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; C067733:testosterone-3-carboxymethyloxime; D013739:Testosterone; C427845:28 kDa gluthathione S-transferase antigen, Schistosoma haematobium; D005982:Glutathione Transferase