Effect of testosterone treatments for varying periods on autoimmune development and on specific infiltrating leukocyte populations in the thyroid gland of obese strain chickens

Spontaneous autoimmune thyroiditis (SAT) is detectable by 2 weeks of age in the obese (OS) strain of chicken, and by 6 weeks virtually all of these animals have severe lymphoid infiltration of the thyroid. During the interval from hatching to 6 weeks of age, testosterone implants were administered for varying periods. All treatment groups were terminated at 6 weeks. Testosterone administered shortly after hatching increased thymus weight, depressed bursa weight, and reduced the severity of SAT, as measured by lymphoid infiltration of the thyroid and circulating thyroglobulin autoantibody concentrations. Birds supplemented with testosterone at later intervals exhibited depressed bursa and thymus weight; however, the severity of SAT was not affected. In a second experiment, the treated group was administered testosterone for the first 2 weeks after hatching. Thyroids were histologically examined at 2 and 6 weeks using a panel of five monoclonal antibodies (anti-Ia, anti-IgM, anti-IgG, anti-T cell, and antithymocyte). Compared with untreated controls, testosterone treatment reduced the frequency of Ia+ cells, T cells, and IgG+ cells in the thyroid. This treatment did not affect the frequency of IgM+ cells, and perhaps slightly increased the frequency of thymocytes. These results suggest that testosterone's suppressive effects are associated with changes in thymic development and effector T-cell and regulator T-cell activity.     

Effect of growth hormone and thyroid hormone on autoimmune thyroiditis in obese chickens

The effect of thyroxine (T₄) and recombinant (rcGH) or purified pituitary-derived (pcGH) chicken growth hormone on the development of spontaneous autoimmune thyroiditis (SAT) was examined in the Obese strain (OS) chicken. Day-old OS chicks were randomly assigned to a control or 1.0 ppm T₄ supplemented diet and a vehicle or 500 μg rcGH/kg BW daily injection, using a 2×2 factorial design. At 4 weeks, sera were analyzed for anti-thyroglobulin autoantibody (TgAAb) using a kinetics-based ELISA. Leucocytic infiltration of the thyroid was assessed using computer-based video imaging techniques. A close correlation between TgAAb and thyroid infiltration was seen with both being decreased (p<0.05) by the T₄/rcGH treatment. Neither the T₄ or rcGH alone produced this effect and the rcGH treatment significantly elevated TgAAb. In a second experiment, all but the control group received 1.0 ppm T₄ supplementation and two of the T₄-treated groups received either 50 or 200 μg pcGH/kg BW by daily injection. As before, T₄/pcGH significantly reduced TgAAb and thyroid infiltration. T₄ alone produced no significant effects. These data support the conclusion that the combined treatment of T₄ and cGH exert an immunomodulatory effect within a strain that is predisposed to autoimmune thyroiditis while GH treatment alone exacerbated the condition. These results also show that video imaging techniques can be used to evaluate the extent of histopathology present within the OS thyroid.     

Target organ susceptibility and autoantibody production in an animal model of spontaneous autoimmune thyroiditis.

F1-hybrids of Obese strain (OS) chickens, afflicted with spontaneous autoimmune thyroiditis (SAT), and normal, inbred CB chickens, do not develop severe thyroiditis. About 50% of these crosses show circulating autoantibodies to thyroglobulin (TgAAb), but the thyroid glands are only slightly infiltrated, suggesting that the target organ is not susceptible to autoimmune attack. In the present study we show that despite this mild infiltration TgAAb are only synthesized by lymphoid cells within the thyroid gland. Furthermore, we demonstrate that immunization with chicken thyroglobulin (Tg) in complete Freund's adjuvant causes severe experimental autoimmune thyroiditis (EAT) in F1(OSxCB) hybrids.     

Genetic background of spontaneous autoimmune thyroiditis in the obese strain of chickens studied in hybrids with an inbred line

To determine the number and function of genes which are responsible for spontaneous autoimmune thyroiditis (SAT) in the obese strain (OS) of chickens we crossed birds of this strain (B15/B15) with those of the inbred CB line (B12/B12). The progeny was analyzed for autoantibodies to thyroglobulin (TgAAb) and for histopathological changes in the thyroid glands. In F1 (OS X CB) hybrids only those animals which derived from CB mothers had circulating TgAAb, the progeny from the reverse combination female OS X male CB was negative. Since the disease is not inherited by OS males only, we conclude that maternal TgAAb, which are transferred from the egg yolk to the embryo, might prevent the immune system of the F1 chickens from TgAAb formation via blocking or eliminating the respective antigens. Those F1 hybrids which have high TgAAb levels in the serum show only little or no thyroiditis. Together with other observations, these data lead to the conclusion that the thyroid gland of the F1 hybrids is not susceptible to TgAAb. This supports previous findings that a genetically determined thyroid abnormality is a prerequisite for the full development of SAT. The low degree of SAT in backcross (F1 X OS) animals and F2 hybrids suggests that several genes are involved in the disease. MHC typing of these generations revealed that the B haplotype affects the time of SAT onset.     

Effects of testosterone on the development of autoimmune thyroiditis in two strains of chicken

The effect of testosterone on organ-specific spontaneous autoimmune thyroiditis (SAT) was examined in two strains of chicken: the Obese (OS) strain, which develops SAT at several weeks of age and the control Special C (Sp. C) strain. Both were originally selected from the C strain and are homozygous for the B13 major histocompatibility haplotype. Testes development and testosterone levels in the OS strain were considerably less than those found in comparably aged birds of the Sp. C strain. Testosterone supplementation of the OS strain significantly decreased thyroid infiltration by lymphocytes while castration of the Sp. C strain significantly enhanced infiltration. These results suggest that testosterone reduces SAT and that the hormonal constitution in both strains of chicken affect the frequency of occurrence and severity of this disorder.     

The effects of dietary vitamin E and selenium deficiencies on plasma thyroid and thymic hormone concentrations in the chicken

Beginning at hatching, male Cornell K strain single comb white leghorn chickens were fed a basal diet, with or without vitamin E (100 IU/kg) and/or selenium (Se, 0.2 ppm). After 3 weeks of treatment, animals fed either the Se-deficient or basal diet had significantly reduced plasma Se-dependent glutathione peroxidase activities when compared to those fed a vitamin E and Se-supplemented diet. Similarly, animals fed the vitamin E-deficient or basal diet had significantly reduced plasma alpha-tocopherol levels. The effect of these treatments on plasma concentrations of thyroid hormones (T(3)/T(4)), growth hormone (GH), and thymic hormone (thymulin) was determined using radioimmunoassay and ELISA. A deficiency in Se, but not in vitamin E, resulted in an increase in plasma T(4) concentrations while plasma T(3) concentrations were decreased. Plasma GH levels showed some fluctuation as a result of the dietary treatments but there was no significant correlation between plasma GH levels and any of the other variables. A significant decrease in plasma thymulin levels was observed in Se-deficient birds compared to those receiving adequate Se in the diet. A vitamin E deficiency had no measurable effect on plasma thymulin levels. From these studies, we conclude that plasma thymulin concentrations directly correlate with plasma T(3) concentrations which are negatively affected by a Se deficiency.     

Effects of thyroxine on the photoperiodic control of energy balance and reproductive status in Siberian hamsters.

Siberian hamsters (Phodopus sungorus sungorus) exhibit a variety of seasonal responses when exposed to short days (SD), including decreases in body weight and fat, gonadal regression, and changes in several nonsteroid serum hormone concentrations. One such SD-induced hormonal change is a modest decrease in serum thyroxine (T4) concentrations. In an attempt to determine any underlying hormonal influences for the SD-induced decreases in body weight and fat, we investigated the possible role of T4 and triiodothyronine (T3). This potential paradoxical effect of these hormones on body weight and fat, as compared with most other rodent species, is not without precedent in Siberian hamsters. Specifically, changes in the gonadal steroids have opposite effects on body weight and fat in Siberian hamsters compared with laboratory rats and mice, and Syrian hamsters. SD serum thyroid hormone concentrations were elevated to long-day (LD) levels via subcutaneous T4 injections. Vehicle- and noninjected controls were included, as well as three similar LD-housed groups. Although we found a trend towards decreased T4 serum concentrations in noninjected control hamsters following 9 weeks of SD exposure, this effect did not reach statistical significance. SD-housed, T4-injected hamsters had similar decreases in body, fat pad, and paired testes weights compared to the SD-housed, vehicle- and noninjected controls despite having LD-like serum T4 and T3 concentrations. Thus, no paradoxical effect of the thyroid hormones on body weight (fat) was found, nor do these hormones appear to play a role in the effects of SDs on reproductive status in this hamster species.     

重组GnRH主动免疫对公猪体重及生长激素和IGF-I的影响

目的:探讨重组GnRH六聚体-麦芽糖结合蛋白(MBP-GnRH-6)主动免疫对公猪体重、生长激素和胰岛素样生长因子-I的影响。方法:7头公猪在9周龄时用重组GnRH主动免疫,17周龄时加强免疫,免疫和屠宰前1天称猪体重,酶联免疫分析法检测血清猪生长激素,放射免疫分析法检测血清IGF-I和睾酮水平,Pearson相关分析血清睾酮与IGF-I的相关性。结果:MBP-GnRH-6主动免疫猪血清睾酮浓度显著地低于阳性对照组(P<0.05),体重显著重于阴性对照组(P<0.05),但不影响公猪血清生长激素水平(P>0.05)。在17~21周龄时,免疫组公猪血清IGF-I浓度显著低于阳性对照组(P<0.05),21~25周龄时免疫组公猪血清IGF-I显著高于阴性对照组(P<0.05)。相关分析表明血清睾酮与IGF-I呈正相关。结论:MBP-GnRH-6主动免疫改变了公猪生长性能,增加体重,其作用途径可能是睾酮通过调控血清IGF-I水平来调控的。     

Vitamin E supplementation modulates cytokine production by thymocytes during murine AIDS

Female C57BL/6 mice were infected with LP-BM5 retrovirus, causing murine AIDS, which is functionally similar to human AIDS. Retrovirus infection targeted the thymus, producing altered T cell differentiation via the dysregulation of thymocyte cytokine production. Human AIDS causes vitamin deficiencies, therefore the effects of dietary vitamin E supplementation were determined on the kinetics of cytokine production by concanavalin A-stimulated thymocytes in uninfected normal mice and mice with murine AIDS. Dietary supplementation, with a 15-fold increase in vitamin E (160 IU/1) in the liquid diet (National Research Council), modulated interleukin-2 (IL) production in both uninfected mice and retrovirus-infected mice. Vitamin E significantly reduced the level of IL-4 secretion in the uninfected mice at 4 and 8 weeks, but not at 12 and 16 weeks. It also significantly reduced IL-4 production, elevated by retrovirus infection. Vitamin E significantly reduced IL-6, and interferon-γ production increased in murine AIDS. The effects of dietary vitamin E on concanavalin A-induced proliferation of thymocytes were consistent with the finding of changes in IL-2 secretion. No effects of dietary vitamin E on thymus weight were observed in uninfected or retrovirus-infected mice, whereas vitamin E significantly increased serum and thymic vitamin E concentration, which had been reduced by retrovirus infection. These data indicate that dietary vitamin E supplementation can modulate cytokine production by thymocytes, affecting T cell differentiation, especially during retrovirus-induced immune dysfunction.     

Changes in the thymus and spleen of the turtle Mauremys caspica after testosterone injection: a morphometric study.

To confirm a possible role of sex hormones in governing the seasonal variations affecting the reptilian lymphoid organs, a morphometric analysis was carried out on the thymus and spleen of turtles, Mauremys caspica, intraperitoneally injected with a single dose of testosterone propionate (TP) at the third week of June when physiological levels of testosterone are low. At 4 and 6 weeks, control turtles show an apparent lymphocyte mobilization both from thymus and spleen with a decrease in the percentage of thymic cortex, numbers of cortical lymphocytes, and mitotic index, but increased numbers of medullary lymphocytes. In the thymic cortex of treated turtles, there is a decrease in the same parameters but they occur in the first 2 weeks, whereas the medullary lymphocytes also undergo reduction at 4 and 6 weeks. In addition, the number of reticuloepithelial cells per area unit decreases at 2 weeks in the thymic cortex of treated turtles. These results are discussed from the point of view of a biphasic effect of testosterone on turtle lymphoid organs: In the first weeks, the changes observed could be attributed to the high levels of testosterone; after 4 and 6 weeks, variations are dependent both on long-term effects of testosterone and on those induced by the high values of corticosterone occurring in summer.     

Melatonin: its antagonism of thyroxine's antisomatotrophic activity in male Syrian hamsters

The effects of daily evening melatonin injections on serum and pituitary levels of growth hormone (GH) and follicle stimulating hormone (FSH) were investigated in male Syrian hamsters receiving thiourea in the drinking water. Melatonin injections, by themselves, had no significant effect on serum or pituitary GH. Thiourea induced hypothyroidism reduced pituitary GH content but increased serum GH several fold. Daily thyroxin (T4) injections for 3 weeks partially restored pituitary GH content and reduced circulating GH to control values. Melatonin injections prevented T4 from reducing circulating GH levels to normal in hamsters receiving thiourea. As previously reported, FSH levels in serum and pituitary were reduced by melatonin. Thiourea-induced hypothyroidism prevented this effect. Daily T4 injections increased circulating FSH levels above control levels; melatonin injections prevented this increase in serum FSH. These observations show that melatonin and T4 have antagonistic actions on GH and FSH release from the pituitary. We conclude that melatonin influences the release of hypothalamic hormones regulating GH and FSH release from the pituitary. The effects of T4 on the sensitivity to melatonin injections could be accounted for by thyroid hormone regulation of pituitary receptors for hypothalamic hormones. An alternative explanation is that T4 regulates the concentration of melatonin receptors in the central nervous system.     

Seminal vesicle and preputial gland response to steroids in adult male mice is influenced by prior intrauterine position.

There are differences in serum steroid concentrations during fetal life between male mice that develop between two male fetuses (2M males, with elevated testosterone) and between two female fetuses (0M males, with elevated estradiol). The present studies were undertaken to determine whether prior intrauterine position would influence the weight of seminal vesicles and preputial glands in adult male mice. To eliminate any potential differences between 2M and 0M males in circulating gonadal steroids, all males were castrated in adulthood and implanted with silastic capsules containing testosterone (T), dihydrotestosterone (DHT) or a combination of T and estradiol-17 beta (E2) or DHT and E2. Three weeks later, preputial glands were significantly heavier in 2M than 0M males after treatment with T but not DHT. Seminal vesicles were also significantly heavier (blotted wet weight) in 2M than 0M males after treatment with T. For 2M males, seminal vesicles weighed the same in response to treatment with T or DHT. However, relative to the effect of T, DHT significantly increased seminal vesicle weight in 0M males such that they were equivalent to weights in 2M males treated with T or DHT. This finding suggests that seminal vesicles in 0M males have lower concentrations of 5 alpha-reductase and, thus, a lower capacity to metabolize T to DHT which is required for normal seminal vesicle function. There were no significant effects of E2 (in combination with T or DHT) on seminal vesicle or preputial gland weight.     

Relationship between circulating thyroid hormones and humoral immunity in immature male chickens

The objective of this experiment was to examine the relationship between levels of circulating T3, T4, and humoral immunity in immature male chickens. Three week old Single Comb White Leghorn male chicks were used as the experimental animals. In order to produce a wide range of circulating thyroid hormone concentrations, birds were divided into groups and received one of nine treatments including surgical thyroidectomy; 0.1% propylthiouracil (PTU) in the feed; 1 ppm T3 and 10 ppm T4 in the feed. Antibody production against sheep red blood cells (SRBC) (thymus-dependent antigen) and Brucella abortus (BA) (thymus-independent antigen) was tested at 6 weeks of age. Concentrations of T3 and T4 were measured in birds from each treatment group at 7 and 11 weeks of age. At 11 weeks of age, birds were weighed, sacrificed and lymphoid organs removed and weighed. There were positive correlations between circulating thyroid hormones and weights of bursa of Fabricius and spleens. There were no significant correlations between circulating thyroid hormones and antibody production. It was concluded that physiological levels of thyroid hormones are needed to maintain normal weights of bursa and spleen. Furthermore, we conclude that lower than physiological levels might be sufficient for normal antibody production. Finally, stimulation of antibody production using thyroid hormones may require different doses than what were utilized in this study.     

The goitre of the BB/O rat: an animal-model for studying the role of immunoglobulins stimulating growth of thyroid cells.

The BB rat is a well-known animal model for the study of autoimmune thyroid disease. Antithyroglobulin antibodies can be detected in the circulation from the age of 6 weeks onwards, and accumulations of lymphoid cells occurs in the thyroid of up to 60% of animals at the age of 20 weeks and over. The rat, however, stays euthyroid, the thyroid is not destroyed, and hence the disease is not yet well characterized. The study reported here shows that the thyroid weights of 41% (40/97) BB rats were raised from week 6 onwards in comparison to those of Wistar controls. Morphologically, BB thyroids showed a strong similarity to the human disease entity 'colloid goitre', namely an active growth, high columnar epithelium, branching and budding of thyrocytes, no signs of thyroid destruction and in 42% of rats at the age of 22-26 weeks, a development of intrathyroidal lymphoid tissue. Plasma TSH was not significantly raised in the animals. For this reason the presence of immunoglobulins which stimulate the growth of thyroid cells (so-called TGI's) was determined in 12-16-week-old BB rats (n = 10) and in control Wistar rats (n = 10). At this time a significant difference could be recorded in thyroid weights between BB/O rats and Wistar controls (20.1 +/- 6.0 mg vs. 15.8 +/- 2.9 mg, respectively), even in the absence of any intrathyroidal lymphoid cell infiltration. Protein-A-Sepharose purified serum IgG of these animals was used to detect TGI-activity via the 'Feulgen Cytochemical Bioassay'. Of the BB/O rats, eight were clearly positive for TGI, all of the Wistar rats were negative. The data show that the autoimmune prone BB rat may thus serve as an animal model for euthyroid goitre associated with thyroid stimulating antibodies.     

Effects of Castration, Depo-Testosterone and Cyproterone Acetate on Lymphocyte T Subsets in Mouse Thymus and Spleen

The effects of testosterone on the relative proportion of Thy 1.2, CD4 (L3T4) and CD8 (Lyt-2) cells in thymus and spleen were studied after castration and administration of Depo-testosterone (DT) separately or together with cyproterone acetate (CA) (an antiandrogen) in BDF1 mice. Injection of 0.5 mg/100 g body weight of DT during 2 weeks decreased significantly the number and proportion of double positive (DP) (CD4+ CD8+) and increased the percentage of single positive (SP) CD4+ (CD4+ CD8-), whereas there was a slight decrease in the Thy 1.2+ cells in the thymus. In parallel, we observed an increase in CD8+ (CD4- CD8+) cells in the spleen. The androgen deprivation after 3 weeks of castration induced a decrease in the percentage of CD4+ cells in thymus and both CD4+ and CD8+ cells in spleen. Injection of CA (0.5 mg/100 g body weight) had the same qualitative effects as DT on the proportion of lymphocyte T subsets in castrated mice. However, the combined activities of DT and CA were greater than either alone. These data indicate the main role of testosterone in the distribution of CD4+ and CD8+ cells in male mice. The similar effects of CA and DT in the lymphoid organs may suggest a difference between androgen receptors of sexual and lymphoid organs.     

Growth hormone secretion in the obese male rat: modulation by the gonadal and thyroid axes.

The present study was designed to determine if either the testes or thyroid plays a role in the blunted GH secretion observed in the obese male rat. Analysis of individual GH secretory profiles in adult lean and obese Zucker rats revealed a severe attenuation of both mean GH levels and individual GH pulse amplitudes in obese rats as well as a significant lowering of circulating testosterone levels. Normalization of the testosterone levels by the use of sc Silastic capsules elevated but did not normalize GH pulse amplitudes in obese animals. Further, the GH response to either rat GH-releasing factor (5 mu/kg) or morphine (1 mg/kg) were reduced in obese male rats. In contrast, the thyroid axis showed minimal change in obese animals. A slight reduction in free T3 levels in serum was observed while free and total T4 and total T3 were normal in obese rats. Further, mean circulating TSH levels and the TSH response to 500 ng/kg TRH were not altered in fat rats. Thus, the reduced GH secretion observed in the obese rat is not paramount to an alteration in either gonadal or thyroid function. This alteration of the GH secretory axis may not be attributable to one factor but more likely caused by a number of concomitant deficits which may act in concert to manifest impaired GH secretion.     

Spontaneous autoimmune thyroiditis in obese strain chickens: a genetic analysis of target organ abnormalities

In this study we investigated the genetic background of primary abnormalities found in the thyroid gland of Obese strain (OS) chickens with spontaneous autoimmune thyroiditis (SAT), i.e., susceptibility to passively transferred antibodies to thyroglobulin (TgAb) and incomplete suppression of iodine uptake by thyroxine (T4). Several crosses between the B15/B15 subline of OS chickens and the inbred CB line (B12/B12) were done and the progeny was analyzed for thyroiditis after injection of OS serum containing high titers of TgAb. It was found that passive transfer of TgAb increased the lymphoid infiltration in the thyroids of OS chickens, but had no effect on CB birds. A genetic analysis of backcrosses revealed that this trait is, in the case of simple Mendelian inheritance, encoded by at least three recessive genes. The thyroidal 131I uptake of these crosses under T4 was also determined and we found that this trait is most probably encoded by only one recessive gene.     

A high iodine intake in Wistar rats results in the development of a thyroid-associated ectopic thymic tissue and is accompanied by a low thyroid autoimmune reactivity.

Evidence is accumulating that dietary iodine intake is an important modulator of autoimmune thyroid reactions. To study this role of iodine intake further, female Wistar rats were kept on an enriched iodine diet (EID, iodine intake 100 micrograms iodine/day) for a period of up to 18 weeks. Control rats were either on a normal iodine diet (NID, iodine intake 7 micrograms iodine/day) or a low iodine diet (LID, 2 days of 1% KClO4 followed by iodine-deficient drinking water/pellets). During the first 6 weeks of the EID rats developed a thyroid-associated ectopic thymic tissue (50-57% of the animals on EID versus 7-14% of NID rats and 0% of LID rats). This thyroid-associated ectopic thymic tissue showed a similar histology (cortex and medulla) and a similar marker pattern as normal rat thymus concerning TdT expression (positive cells in the cortex) and CD4/CD8 positivity (double-positive cells in the cortex, single-positive cells in the medulla). The excessive iodine diet also resulted in a lowered thyroid autoimmune reactivity as compared to the NID and LID, viz. (1) in a lower incidence of anti-colloid antibodies in serum (12.5% positivity in EID rats versus 36% in NID and 60% in LID rats at 18 weeks) and (2) lower numbers of intrathyroidal lymphoid cells, viz. lower numbers of dendritic cells and lower numbers of CD4 and CD8 positive lymphocytes. It is hypothesized that the development of the thyroid-associated ectopic thymic tissue in the EID rats is related to their low thyroid autoimmune responsiveness; the tissue might play a role in tolerance induction to thyroidal autoantigens.     

The effects of a monoclonal antibody to interferon-γ on experimental autoimmune thyroiditis (EAT): prevention of disease and decrease of EAT-specific T cells

CBA/J mice immunized with thyreoglobulin (Tg) develop an experimental autoimmune thyroiditis (EAT) with lymphocytic infiltration of the thyroid glands, autoantibodies to Tg and occurrence of EAT-specific T cells. When these mice were treated for 4 weeks after immunization with 1 mg/week of a monoclonal antibody (mAb) that neutralizes the activity of interferon-γ (IFN) a beneficial effect on the onset of EAT was observed. Characteristic features of EAT were significantly reduced, including the lymphocytic infiltrations of the thyroid glands and the serum levels of autoantibodies to Tg. Moreover, in lymphoid organs, mAb to IFN-γ significantly reduced the percentages of Tg-specific CD8⁺ cells, labeled by the anti-clonotypic mAb AG7. These Tg-specific T cells seem responsible for thyroid damages and disease development, since EAT was simultaneously abrogated. These results show that IFN-γ plays an essential role in the pathophysiology of EAT and suggest the possibility to treat autoimmune thyroid diseases with mAb to IFN-γ or drugs able to antagonize the production and/or the action of this cytokine.     

Endocrine disruptions induced by artificial induction of mercury chloride on sea bream

There are a large number of chemicals, which are released into the Persian Gulf, capable of interfering with the synthesis and action of natural thyroid and testosterone hormones. These are considered as endocrine disruptors. In the present study, sea bream was exposed to four different concentrations (10, 20, 40, 80 μg l^?1) of the widely used mercury chloride in a laboratory condition, and effects on the concentrations of serum testosterone and thyroid (T3 and T4) were assayed. Mercury chloride exhibited significant effects on both T3 and T4 (P?<?0.5) concentration of serum. No significant changes occurred in the concentration of serum testosterone (P?>?0.5); however, exposure to higher mercury chloride concentration showed suppressive effects on serum testosterone. Results of the present experiment indicated that mercury chloride induced alteration in the structure of the gonad and thyroid and can be considered as an endocrine disruptor substance in yellowfin sea bream.