Hypogonadism and ecdysteroid production in Loa loa and Mansonella perstans filariasis.

Possible endocrinological repercussions of infection with Loa loa and Mansonella perstans filariae were studied in Gabonese subjects. Microfilaremic males were compared with amicrofilaremic controls. In the infected group 13/105 subjects (12%) presented only abnormally low serum levels of testosterone (less than 4 ng/ml), 25/105 (24%) only abnormally high serum levels of gonadotrophins, FSH (greater than 15 mIU/ml) and LH (greater than 20 mIU/ml), and 22/105 (21%) presented anomalies in both testosterone and gonadotrophin levels. One out of 68 control subjects had 3.6 ng/ml seric testosterone and all had normal levels of gonadotrophins. Ecdysteroids were detected (greater than 0.025 ng/ml) in the serum of 87/97 (90%) microfilaremic subjects (GM 0.123 ng/ml) compared to 12/64 (19%) controls (GM 0.030 ng/ml). Ecdysteroids were detected in the urine of all subjects, infected (GM 8.468 ng/ml) as well as control (GM 1.245 ng/ml). The hormonal perturbations were correlated with the levels of Loa loa microfilaremia but not with those of serum and urinary ecdysteroids. These results demonstrate that microfilaremic subjects often show endocrinal signs of hypogonadism and present appreciable levels of ecdysteroids in serum and urine. A direct role for parasitic ecdysteroids in hypogonadism remains to be demonstrated.

Fundamental aspects and potential roles of ecdysteroids in schistosomes an update overview.

The human digenic trematodeSchistosoma mansoni produces ecdysteroid hormones. Both ecdysone (22R)-2ß,3ß,14,22,25-pentahydroxy-cholest-7-en-6-one and 20-hydroxyecdysone (22R)-2ß,3ß, 14,20,22,25-hexahydroxycholest-7-en-6-one were detected during the critical development stages of this bisexual parasite: during the exponential growth phase to adult stage (day 11 postinfection) and during the sexual maturation of adult and egg laying (day 40 postinfection). The parasites released their ecdysteroid hormones in the biological fluids of the infected vertebrates as soon as six days postinfection. In addition, the time course of the ecdysteroid titer was correlated with the susceptibility or the innate resistance of the host to schistosome infection. Moreover, we demonstrated that after a schistomicide therapy, ecdysteroids from urine of infected children decreased markedly four days after drug administration. We also have demonstrated that immunization of rodents with an ecdysone-BSA complex led to the reduction of the worm burden. By in vitro studies, we have shown that the ecdysterone antibodies were able to kill the juvenile worms within 24 hr. In addition, we have demonstrated that the enzymes Superoxide dismutase (SOD, EC 1.15.1.1) were present in schistosomes and that the total Superoxide dismutase activities in both males and females could be correlated with the 20-hydroxyecdysone within parasites.

Excretion of ecdysteroids by schistosomes as a marker of parasite infection.

Ecdysteroids produced by schistosomes are released in biological fluids of infected hosts. In the sera, the concentration of ecdysteroids correlates with the permissiveness of the host to schistosome infection and its detection is available in the absence of positive parasitological tests. In the urine, ecdysteroid concentration decreases markedly after chemotherapy. 20-Hydroxyecdysone and its epimer were identified in the urine of infected patients using mass spectrometry. These data demonstrate for the first time that ecdysteroids are released by organisms. Moreover, they are potent molecules of parasite infection and can be used for parasite diagnosis.

Ecdysone and 20 hydroxyecdysone: new hormones for the human parasite schistosoma mansoni.

The insect moulting hormones, ecdysone and 20 hydroxyecdysone, were detected by the combined use of radioimmunoassay and high performance liquid chromatography in the human parasite Schistosoma mansoni. On day 11 after infection only the ecdysone form is present, but, on day 40 after infection the ratio between ecdysone and 20 hydroxyecdysone changes with anatomic localization of the adult worms in mammalian host. In the eggs, the ratio of these two hormones is identical to the ratio found in sexually mature worms located in mesenteric veins. These data demonstrate for the first time that S. mansoni synthesizes the steroid hormones ecdysone and 20 OH ecdysone which are potent molecules in stimulating growth and vitello-genesis of this gonochoric trematode.

Radioimmunoassay of insect juvenile hormones and of their diol derivatives.

We have developed a radioimmunoassay for insect juvenile hormones. The C18 hormone (JH I) was first converted into diol by opening the 10, 11-epoxy ring. Diol was then succinylated and coupled to human serum albumin to make it immunogenic. High titer antisera were obtained from immunized rabbits. Succinyl juvenile hormone was also coupled to the peptide glycyltyrosine and iodinated so as to form a water-soluble 125I-labelled analogue well recognized by antibodies (60% bound by the 1/2000 000 dilution of antiserum routinely used in radioimmunoassay). Standards and biological samples were treated with acidic dioxane in order to convert each hormone into its corresponding diol. In this way, the sensitivity threshold of the radioimmunoassay was under 0.015 pmol. All three diols were equally recognized by the antibodies. Hormones JH I, JH II and JH III could be assayed separately as diols after thin-layer chromatography or high-pressure liquid chromatography purification of the biological samples. This method was used to determine physiological levels of juvenile hormones in the haemolymph of several insects at different development stages including embryos and in corpora allata cultures.