Functional Specific Binding of Testosterone toSchistosoma haematobium28-Kilodalton GlutathioneS-Transferase

Abstract

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 ؋ 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.Sex hormones seem to have an influence on the level of parasitic infection. Indeed, gender-dependent patterns of prevalence and intensity of infection after puberty have been observed for several parasite species (5). It has been suggested that this effect seems to be associated with the regulatory roles of sex steroids on antiparasite immunity (2, 24). Generally, female hormones have an influence in increasing antibody response against specific antigen, which could explain the higher resistance of women against several parasitic infections (24, 25).During human Schistosoma infection, a chronic infection affecting 200 million individuals around the world, sex hormones and particularly the high level of testosterone after puberty could be an important immune modulator leading to the decrease of susceptibility to infection with age (10, 26). In mice infected by Schistosoma mansoni, fewer adult worms develop in males than in similarly infected females (9). In addition, female mice treated with testosterone before infection presented a reduction in worm burden, whereas no difference in antischistosome immune response was detected between treated and untreated animals (20). These authors suggest thus that effects of testosterone on specific immunity are not adequate to explain the differences in parasite loads observed between the sexes.Schistosomes could express a hormone receptor with homology to the testosterone receptor, which could explain the direct effect of testosterone on worm development (8). Interestingly, it has been demonstrated that testosterone treatment can affect not only the development of Nippostrongylus brasiliensis helminthic worms but als...

Steroids in aquatic invertebrates

“…A role of these steroids in sexual development was proposed based on metabolic studies (Briggs 1972) and on the effects of exogenous steroids or steroid synthesis inhibitors on fecundity (Morrison et al 1986), but experimental evidence was limited. A surprising explanation of the decrease of fecundity evoked by exogenous testosterone could be the specific binding of this steroid to glutathione S-transferase, resulting in the inhibition of this important detoxification enzyme (Remoué et al 2002). More recently (Verjovski-Almeida et al 2003), genomic studies on the human parasite S. mansoni have allowed to find transcripts for a 17b-HSD and a testosterone 6b-hydroxylase, together with some receptor elements (e.g., an estrogenrelated receptor), thus providing a basis for future investigations (whatever steroids would have an endogenous origin or come from the vertebrate host).…”

A New Parasiticidal Compound inT. soliumCysticercosis

“…As it can be seen, direct effects of sex steroids upon helminth parasites (cestodes, nematodes, and trematodes) and protozoan parasites are not unusual. In fact, previous results suggest that these pathogens not only are directly affected by adrenal hormones, but they have also developed several strategies to exploit the host's endocrine microenvironment [22, 23], which include degradation of host proteins as an alternative source of amino acids [24], development of parasitic-sex steroid receptors [25, 26], and cross-activation of signal transduction pathways [27, 28]. …”

Progesterone Induces Scolex Evagination of the Human ParasiteTaenia solium: Evolutionary Implications to the Host-Parasite Relationship

“…The latter interacts with two main progesterone receptor (PR) isoforms [28], whereas other hormones such as androgens only have one specific receptor [26]. Interestingly, a similar mechanism could occur also in parasites [21, 29, 30]. …”