Developmental exposure to pentachlorophenol affects the expression of thyroid hormone receptor beta1 and synapsin I in brain, resulting in thyroid function vulnerability in rats.

Pentachlorophenol (PCP), a component of biocides and a contaminant in diverse tissue samples from humans from various geographic areas, disrupts regulatory effects of thyroid hormones. Here we examined the effects of developmental exposure of rats to PCP on various aspects of brain development, male reproductive function, and adrenal function, all of which are under thyroid hormones regulation. PCP was administered to dams and their offspring via drinking water (6.6 mg l(-1)) during gestation and lactation. Tissue samples were obtained from dams, 3-week-old weanling pups, and 12-week-old pups. Gene expressions of thyroid hormone receptor beta1 and synapsin I, factors that promote brain growth, was increased in the cerebral cortex of PCP-treated weanling females, whereas plasma concentrations of total thyroxine were decreased in dams and weanling pups, and plasma thyroid-stimulating hormone concentrations were higher in PCP-treated weanling males. PCP caused a decrease in plasma corticosterone concentrations in 12-week-old female rats, but not in male rats or weanling females. PCP-treated male pups had significantly increased testis weight at 12 week of age. No overt signs of toxicity were noted throughout this study. Our results show that PCP exposure during development causes thyroid function vulnerability, testicular hypertrophy in adults, and aberrations of brain gene expression.

Effect of methimazole-induced hypothyroidism on adrenal and gonadal functions in male Japanese quail (Coturnix japonica).

To investigate the effect of hypothyroidism on gonadal and adrenal functions in male Japanese quail (Coturnix japonica), hypothyroidism was induced in male adult Japanese quail by daily administration of 2-Mercapto-1-methylimidazole (methimazole) in their drinking water. Four weeks after methimazole treatment, the Japanese quail were sacrificed, and the plasma concentrations of free triiodothyronine (FT3), free thyroxine (FT4), total T3 (TT3), total T4 (TT4), corticosterone, testosterone, LH and immunoreactive (ir) inhibins were measured by radioimmunoassay, the testes and adrenal glands were removed and weighed and the thyroid glands and testes were fixed in 4% paraformaldehyde for histological observation. The results showed that the hypothyroidism induced by methimazole caused a significant decrease in body and testes weight; the plasma levels of FT3, FT4 and TT4 significantly decreased, and the hypothyroid quail possessed a greater number of small follicles and more follicular epithelial cells in the thyroid gland. In addition, hypothyroidism resulted in a significant decrease in the plasma concentrations of corticosterone, LH, testosterone and ir-inhibin. Furthermore, no spermatogenesis was found in the seminiferous tubules of the methimazole treatment groups. These results clearly demonstrate that hypothyroidism caused both gonadal and adrenal disturbances in the adult male Japanese quail.

Effects of hypothyroidism on gonadal function after transition of short day photoperiod in male golden hamsters (Mesocricetus auratus).

Thyroid hormones permit the annual reproductive transition of seasonal breeders. Although, precise function of thyroid hormones in seasonal breeding is not well understood. In the present study, we examined effects of hypothyroidism on the hypothalamus-pituitary-gonadal axis in adult male golden hamsters after transition of the short-day photoperiod (SD; 8 h light: 16 h dark) condition. We confirmed that hypothyroid, which had been induced by administration of thiouracil in drinking water for 4 weeks, did not have direct effects on testes in male hamsters under the long-day photoperiod. Plasma concentrations of free T3 and T4 decreased 15 weeks after transition of SD condition. Plasma concentrations of testosterone in the hypothyroid group decreased earlier than in the control group after the transition from LD to SD. In animals treated with testosterone after castration, plasma concentrations of LH in the hypothyroid group decreased earlier than in the control group after the transition of SD. On the other hand, pituitary response to GnRH for LH release did not change in castrated hamsters as a result of hypothyroidism. These results suggest that thyroid hormones act the hypothalamus and might be required to maintain GnRH secretion in male golden hamsters.

Inhibin secretion in the golden hamster (Mesocricetus auratus) testis during active and inactive states of spermatogenesis induced by the restriction of photoperiod.

Gonadal function in the male golden hamster (Mesocricetus auratus) was investigated during exposure to a short photoperiod condition. Within 3 weeks of exposure to the short photoperiod condition, FSH and testosterone in the plasma significantly decreased, and subsequently immunoreactive (ir)-inhibin significantly decreased. Testicular contents of ir-inhibin and testosterone, and pituitary contents of LH and FSH also significantly decreased by 3 weeks with regression of weight of testes, epididymis and seminal vesicles and sperm head count. Circulating LH varied but not significantly. Thereafter, all reproductive parameters and secretion of LH, FSH, ir-inhibin and testosterone gradually recovered after 17 weeks of exposure even though animals continued to be subjected to the short photoperiod condition. Plasma concentrations of inhibin B and inhibin pro-alphaC were detectable and were significantly decreased after 15 weeks of exposure to the short photoperiod, but their levels were still detectable. Immunopositive reaction of inhibin alpha and betaB subunits was found in Sertoli cells and Leydig cells in the regressed testes of animals subjected to short photoperiod as was also seen in animals before exposure to the short photoperiod. Although the spermatogenic cycle was suppressed like prepubertal animals, the present study showed that the testicular recovery, so-called refractoriness, is functionally different from the developing stage of immature animals, especially with regard to inhibin secretion. The present results showed that changes in FSH preceded changes in inhibin during the regression and recovery phases, indicating that FSH is a major regulatory factor of inhibin secretion in male golden hamsters. The present study also demonstrated that regressed testes still secrete a small amount of bioactive inhibin during exposure to a short-photoperiod condition.

Inhibin B regulating follicle-stimulating hormone secretion during testicular recrudescence in the male golden hamster.

In the present study, to clarify whether inhibin affects follicle-stimulating hormone (FSH) secretion in the recrudescence of the male golden hamster, we used a recently developed specific enzyme-linked immunosorbent assay (ELISA) in order to measure 2 forms of inhibin molecules: inhibin B and inhibin pro-alphaC. In addition, we used the radioimmunoassay (RIA) to measure immunoreactive (ir-)inhibin, FSH, luteinizing hormone (LH), and testosterone. And finally, we used the proliferating cell nuclear antigen (PCNA) and computer-assisted sperm motion analysis (CASA) methods to ascertain how well spermatogenesis and sperm motility recover from the photoinhibition caused by exposure to a short-day (SD; 10-hour light: 14-hour dark) photoperiod. Animals were exposed to SD for 15 weeks, and then their testes were checked carefully and found to be completely regressed. Thereafter, those animals were transported to a long-day (LD; 14-hour light: 10-hour dark) photoperiod. Sampling was carried out at weeks 0 (exposed SD 15 weeks), 1, 2, 4, 6, 8, and 10. Plasma FSH rapidly increased and reached peak levels 2 weeks after transferral to the LD photoperiod and then declined to normal LD levels at week 6. Circulating ir-inhibin, inhibin B, and inhibin pro-alphaC rose to normal LD levels by week 4. A highly significant inverse correlation was observed between plasma FSH and inhibin B but not between FSH and either ir-inhibin or inhibin pro-alphaC. Plasma testosterone recovered to normal LD levels within 1 week. Sperm motility parameters were low until week 2 and recovered to normal LD levels from weeks 4 to 10. PCNA-labeled cells were confined to the spermatogenic cells of the seminiferous tubules, though Leydig and Sertoli cell nuclei were never stained for PCNA during the period studied. The number of pachytene spermatocytes and the diameter of seminiferous tubules increased in a time-dependent manner after transferral from SD to LD. In conclusion, these results suggest that 1) secretion of inhibin B may be stimulated by an early rise in FSH; 2) inhibin B suppresses FSH secretion from weeks 2 to 10, after transferral to the LD photoperiod; and 3) testes recrudescence is based on the increase in the number of sperm cells instead of the increase in the number of Sertoli and Leydig cells of the male golden hamster.