Synthesis of sex steroids by
The host’s hormonal environment determines the susceptibility, the course, and severity of several parasite infections. In most cases the infection disturbs the host environment, and activates immune responses that end up affecting the endocrine system. In the other hand, a number of reports indicate that parasites have reproductive systems, and some others have shown that these organisms synthetize sex steroid hormones. We have shown that cysticerci, the larval stage of Taenia solium and Taenia crassiceps ORF and WFU, synthesize steroid hormones. This capacity was modified by drugs that act inhibiting the steroid synthesizing enzymes, or blocking the parasite’s hormone receptors. We have also shown that the cysticerci of T. crassiceps WFU and T. solium have the capacity to synthesize corticosteroids as deoxicorticosterone and corticosterone. We also reviewed the effects of insulin on these parasites, and the receptors found for this hormone. A deep knowledge of the parasite’s endocrine properties will contribute to understand their reproduction and the reciprocal interactions with the host. Likewise, may also help designing tools to combat the infection in clinical situations.
Corticosteroids and sex steroids are crucial in vertebrate reproduction, metabolism and immune response, but their role in invertebrates had received a reduced attention, similarly happen with the influence of peptides and protein hormones in parasite’s development. Therefore, we review here the parasite-endocrine system interplays.
The interaction between parasites and the host defines the intensity of parasite infections. In many cases, the presence of parasites in the host changes its endocrine equilibrium due to the activation of the immune system response, which finally affects the host endocrine system through the influence of cytokines and growth factors released by the immune cells. These changes sometimes control the infection, but in many cases the immune system of the host cannot reject the parasite invasion and thereafter the organisms succeed, and rapidly multiply in the host. A role for 17-beta-estradiol in immunoendocrine regulation of murine cysticercosis by
Some parasite infections disrupt the host endocrine system, to this regards we recently reported that the chronic infection of female mice with
In some cases, the parasite’s infection affects the host reproductive behavior, for example, changes in reproductive behavior occurred in
1.1 Sex steroids effects
Several reports indicate the host hormonal environment determines the susceptibility, the course, and severity of many parasite infections. Supporting this fact, a clear dichotomy in infection susceptibility between males and females had been observed in some parasitic infections. For example, the rich estrogen environment provided by female mice facilitates
In addition, steroids may directly influence the growth and proliferation of parasites. For example,
Particularly estrogens are important for
The presence of steroid receptors in parasites have been documented , hence the blockage of steroids receptors might mitigate the effect of these hormones. For example, the expression of an estrogen binding protein similar to nuclear estrogen receptor was shown in
Interventions on the sex steroid receptors affect the
1.2 Corticosteroids are key hormones in the host-parasite interplay
Corticosteroids are synthesized in the adrenal cortex and are classified as glucocorticoids, mineralocorticoids and adrenal androgens. Cortisol and corticosterone are the main glucocorticoids and are involved in glucose, lipid and protein metabolism. Aldosterone and dexycorticosterone (DOC) are classified as mineralocorticoids because they participate in the hydro-electrolytic balance, whereas adrenal androgens as dehydroepiandrosterone (DHEA) take part in the pubertal process. DHEA is an estrogen precursor that can be transformed to potent androgens in the testis and is an important immune regulator .
Cortisol and corticosterone are key hormones in the physiological stress response (in example exercise), and in non-physiological stress situations, such as social isolation, persecution, infections, etc., all circumstances that increase serum corticosteroids levels. It is now generally accepted that prolonged stress conducts to impairment of the immune response.
1.2.1 Corticosteroid use in neurocysticercosis
Corticosteroids are employed to prevent or modulate the brain inflammation that follows anthelmintic treatment of parasitic cysts with cysticidal drugs as albendazole or praziquantel [14, 15, 16]. The absence of corticosteroids administration in the cysticidal treatment initiates an acute immune response to the parasite that conducts to serious clinical symptoms as seizures, brain edema, and death. These side effects are caused by neuroinflammation and are effectively managed with corticosteroids. On the other side, the administration of dexamethasone plus albendazol to Balb/c mice reduced the cysticidal effect of albendazole .
In vitroeffects of glucocorticoids on parasite growth and viability
It had been shown that corticosteroids may directly influence parasite’s proliferation and metabolism. For instance, we had shown that corticosterone and dexamethasone increase the capacity of
Taenia soliumand crassicpessynthesize steroid hormones
1.3.1 Sex steroids and corticosteroids
The adult worm of
|Radioactive precursor metaboliteS||Transformation rate evaluated in two developmental stages of |
|Invaginated cysticerci||Evaginated cysticerci|
|6 hours||9.6 ± 2.1||22.9 ± 1.9**|
|24 hours||71.4 ± 7.6||75.5 ± 4.5|
|43 hours||75.0 ± 4.7||74.1 ± 5.3|
|6 hours||7.7 ± 2.7||5.3 ± 3.3|
|24 hours||4.7 ± 2.7||3.8 ± 4.3|
|43 hours||3.1 ± 2.5||0.1 ± 0.5|
Our group have also examined the capacity of
Taenia soliumand Taenia crassicepsand steroidogenic enzymes. Repurposed drugs affect the capacity of parasites to synthesize hormones
Tritiated androstenediol and testosterone were recovered from the culture media of
The effect of enzyme inhibitors on the steroid synthesis by
We have recently shown that
1.4 Additional hormones studied in
T. soliumand Taenia crassiceps
Insulin is a potent metabolic hormone that exerts a wide variety of effects. The main metabolic effect of insulin is to stimulate glucose uptake and utilization in muscle and fat tissue, but this hormone also increases lipogenesis, and even acts on protein synthesis. Insulin signaling through insulin receptors (IR) is an ancient and well conserved pathway in metazoan cells organized as transmembrane proteins with tyrosine kinase activity. To note, the uptake and metabolism of glucose is crucial for
We have shown that incubation of
Using genome-wide screening Wang et al.  identified putative insulin-like peptides in several parasitic platyhelmths as
The effect of human chorionic gonadotropin (hCG) on the growth and proliferation of larval stages of
The interaction between parasites and the host defines the intensity of parasite infections. Steroid hormones play an important role in this interplay. Sex steroids and corticosteroids modify
Thanks to Rangel-Rivera Omar for his technical contribution with Figures and Table.
Conflict of interest
The authors declare that they have no known conflict of interests or personal relationships that could have appeared to influence the work reported in this chapter.