Atsushi Tohei

Bisphenol A inhibits testicular functions and increases luteinizing hormone secretion in adult male rats.

Effects of a xenoblotic estrogen, bisphenol A (BPA), on reproductive functions were investigated using adult male rats. BPA was dissolved into sesame oil and injected sc every day (1 mg/rat) for 14 days. Animals were killed by decapitation after the final administration of BPA, and the trunk blood, pituitary, and testes were collected. Plasma concentrations of prolactin were dramatically Increased and pituitary contents of prolactin were slightly increased in the BPA group compared to the control group. Plasma concentrations of testosterone were decreased and plasma concentrations of LH were increased in BPA-treated rats compared to control rats. Testicular contents of inhibin were decreased in BPA-treated rats compared to control rats, although plasma concentrations of inhibin were not changed after administration of BPA. The testicular response to hCG for progesterone and testosterone release was decreased in BPA-treated rats. Administration of BPA did not change the pituitary response to luteinizing hormone-releasing hormone (LH-RH) in castrated male rats treated with testosterone. Male sexual behavior also was not changed as a result of BPA treatment. These results suggest that BPA directly inhibits testicular functions and the increased level of plasma LH is probably due to a reduction in the negative feedback regulation by testosterone. The testis is probably a more sensitive site for BPA action than the hypothalamus–pitultary axis.

Plasma ACTH levels during early, two-way avoidance acquisition in high- and low-avoidance rats (Hatano strains).

Having successfully bred for high- and low-avoidance rats (HAA and LAA, respectively) on a shuttlebox task, we performed three experiments designed to identify factors which might be related to the phenotypic differences seen in avoidance behavior. In experiment 1, shuttlebox behavior was measured to determine whether the phenotypic difference was activity related. In terms of intertrial responses, there was no difference between HAA and LAA rats in locomotor activity during the conditioning process. Experiment 2 compared adrenal weights of HAA and LAA rats at 11 weeks of age. The observation that the adrenal glands were heavier in HAA than in LAA rats suggested that these strains might differ in aspects of endocrine response. In experiment 3, plasma levels of ACTH and corticosterone were determined during early escape/avoidance acquisition in the shuttlebox. Plasma levels of ACTH after the shuttlebox testing were higher in HAA than in LAA rats. There was no difference between the two strains in plasma levels of corticosterone after testing, possibly due to a ceiling effect. These results suggest that the phenotypic differences in the acquisition of avoidance behavior of HAA and LAA rats may be related to different endocrine responses, rather than to locomotor activity.

Postnatal behavior in Hatano high- and low-avoidance rats following prenatal exposure to low-dose methylazoxymethanol

The hypothesis that genetic factors influence behavioral effects was tested in rats exposed prenatally to methylazoxymethanol (MAM). We examined whether baseline behavior is an important factor influencing behavioral effects, and whether a behaviorally selected strain was useful for study of neurobehavioral teratology. Pregnant high- and low-avoidance animals (HAAs and LAAs) of the Hatano strain, selectively bred for high and low shuttlebox avoidance responses, respectively, were given an IP injection of a low dose of MAM (15 mg/kg) on day 14 of gestation. The offspring of these animals were subjected to behavioral tests for locomotor activity (running-wheel and open-field tests) and learning ability (Biel maze and shuttlebox avoidance tests). There were no significant effects of MAM on running-wheel activity or shuttlebox avoidance learning, whereas the number of errors in the Biel maze was increased in the MAM offspring of both strains. Interestingly, open-field activity of the MAM offspring was markedly decreased in LAAs but not in HAAs. Therefore, an additional experiment was performed to determine plasma levels of ACTH and corticosterone following open-field exposure. When compared to control offspring of the respective strains, plasma levels of ACTH and corticosterone were not altered by prenatal MAM treatment in LAAs. Instead, the MAM offspring in HAAs exhibited decreased ACTH levels in absence of behavioral alterations. These results demonstrated that prenatal exposure to low doses of MAM may alter postnatal behavior and endocrine response of the offspring, although to a differing degree in HAAs and LAAs. Our observations suggested that behaviorally selected strains are sensitive to neurobehavioral teratogens such as MAM.