Biomedical subjects

Shigeru Ohta

Publications and source records attributed to Shigeru Ohta.

At least 37 records · Page 2Linked to original sources

PubMed2005

Potent estrogen receptor ligands based on bisphenols with a globular hydrophobic core.

Candidate estrogen receptor (ER) ligands with two phenolic residues on a three-dimensional hydrophobic core structure (carborane, bicyclo[2.2.2]octene, or adamantane) were synthesized and biologically evaluated. The biological properties of the ligands were markedly dependent on the nature of the hydrophobic core structure. Bis(4-hydroxyphenyl)-o-carborane (6) was a partial agonist/antagonist for ER. 1,2-Bis(4-hydroxyphenyl)bicyclo[2.2.2]octene (10) exhibited potent agonist activity for ER, even though the two phenolic groups are located similarly to those of 6.

Adamantane↗

PubMed2005

Involvement of molybdenum hydroxylases in reductive metabolism of nitro polycyclic aromatic hydrocarbons in mammalian skin.

Molybdenum hydroxylases, aldehyde oxidase and xanthine oxidoreductase, were shown to be involved in the nitroreduction of 2-nitrofluorene (NF), 1-nitropyrene, and 4-nitrobiphenyl, environmental pollutants, in the skin of various mammalian species. NF was reduced to 2-aminofluorene by hamster skin cytosol in the presence of 2-hydroxypyrimidine, 4-hydroxypyrimidine, N(1)-methylnicotinamide, or benzaldehyde, but not hypoxanthine or xanthine. Inhibitors of aldehyde oxidase markedly inhibited these nitroreductase activities, but oxypurinol, an inhibitor of xanthine oxidoreductase, had little effect. In DEAE column chromatography of hamster skin cytosol, the major fraction exhibiting nitroreductase activity also showed aldehyde oxidase activity. 2-Hydroxypyrimidine-linked nitroreductase activities of skin cytosol from rabbits and guinea pigs were also inhibited by an inhibitor of aldehyde oxidase. In contrast, nitroreductase activities of skin cytosols of rats and mice were markedly inhibited by oxypurinol. When aldehyde oxidase activity was estimated in skin cytosol of various mammals using benzaldehyde oxidase activity as a marker, considerable variability of the activity was found. The highest activity was observed with hamsters, and the lowest activity with rats. On the other hand, the highest xanthine oxidoreductase activity was observed with rats, and the lowest activity with rabbits. These skin cytosols of various mammals also exhibited significant 2-hydroxypyrimidine-linked nitroreductase activities toward 1-nitropyrene and 4-nitrobiphenyl catalyzed by aldehyde oxidase and xanthine oxidoreductase. Thus, NF was mainly reduced by aldehyde oxidase and xanthine oxidoreductase in skins of animals. However, the contributions of these two molybdenum hydroxylases were considerably different among animal species.

Aldehyde Oxidase↗

PubMed2005

Metabolism of the alpha,beta-unsaturated ketones, chalcone and trans-4-phenyl-3-buten-2-one, by rat liver microsomes and estrogenic activity of the metabolites.

When chalcone and trans-4-phenyl-3-buten-2-one (PBO) were incubated with liver microsomes of untreated rats in the presence of NADPH, 4-hydroxychalcone and trans-4-(4-hydroxyphenyl)-3-buten-2-one (4-OH-PBO), respectively, were formed as major metabolites. Two minor metabolites of chalcone, 4'-hydroxychalcone and 2-hydroxychalcone, were also observed. The oxidase activity affording 4-hydroxychalcone was inhibited by SKF 525-A, disulfiram, ketoconazole, and alpha-naphthoflavone. The oxidase activities leading to 4-hydroxychalcone and 4'-hydroxychalcone were enhanced in liver microsomes of 3-methylcholanthrene- and phenobarbital-treated rats, respectively. The activity generating 2-hydroxychalcone was enhanced in liver microsomes of 3-methylcholanthrene- and dexamethasone-treated rats. The oxidation of PBO to 4-OH-PBO was inhibited by SKF 525-A, ketoconazole, disulfiram, and sulfaphenazole. This activity was enhanced in liver microsomes of 3-methylcholanthrene-, acetone- and phenobarbital-treated rats. 4-Hydroxylation, 4'-hydroxylation, and 2-hydroxylation of chalcone were catalyzed by rat recombinant cytochrome P450 1A1, 1A2, and 2C6; by 1A1 and 2C6; and by 1A1 and 3A1, respectively. PBO was oxidized by cytochrome P450 1A1, 1A2, 2C6, and 2E1. Chalcone and PBO were negative in an estrogen reporter assay using estrogen-responsive human breast cancer cell line MCF-7. However, 4-hydroxychalcone, 2-hydroxychalcone, 4'-hydroxychalcone, and 4-OH-PBO exhibited estrogenic activity.

Animals↗

PubMed2005

Thyroid hormone-like and estrogenic activity of hydroxylated PCBs in cell culture.

The thyroid hormone-disrupting activity of hydroxylated PCBs was examined. 4-Hydroxy-2,2',3,4',5,5'-hexachlorobiphenyl (4-OH-2,2',3,4',5,5'-HxCB), 4-hydroxy-3,3',4',5-tetrachlorobiphenyl (4-OH-3,3',4',5-TCB) and 4,4'-dihydroxy-3,3',5,5'-tetrachlorobiphenyl (4,4'-diOH-3,3',5,5'-TCB), which have been detected as metabolites of PCBs in animals and humans, and six other 4-hydroxylated PCBs markedly inhibited the binding of triiodothyronine (1x10(-10)M) to thyroid hormone receptor (TR) in the concentration range of 1 x 10(-6) to 1 x 10(-4) M. However, 4-hydroxy-2',4',6'-trichlorobiphenyl (4-OH-2',4',6'-TCB), 3-hydroxy-2,2',5,5'-tetrachlorobiphenyl, 4-hydroxy-2,2',5,5'-tetrachlorobiphenyl, 4-hydroxy-2,3,3',4'-tetrachlorobiphenyl, 2,3',5,5'-tetrachlorobiphenyl and 2,3',4',5,5'-pentachlorodiphenyl did not show affinity for TR. The thyroid hormonal activity of PCBs was also examined using rat pituitary cell line GH3 cells, which grow and release growth hormone in a thyroid hormone-dependent manner. 4-OH-2,2',3,4',5,5'-HxCB, 4,4'-diOH-3,3',5,5'-TCB and 4-OH-3,3',4',5-TCB enhanced the proliferation of GH3 cells and stimulated their production of growth hormone in the concentration range of 1 x 10(-7) to 1 x 10(-4) M, while PCBs which had no affinity for thyroid hormone receptor were inactive. In contrast, only 4-OH-2',4',6'-TCB exhibited a significant estrogenic activity using estrogen-responsive reporter assay in MCF-7 cells. However, the 3,5-dichloro substitution of 4-hydroxylated PCBs markedly decreased the estrogenic activity. These results suggest that, at least for the 17 PCB congeners and hydroxylated metabolites tested, a 4-hydroxyl group in PCBs is essential for thyroid hormonal and estrogenic activities, and that 3,5-dichloro substitution favors thyroid hormonal activity, but not estrogenic activity.

Animals↗

PubMed2005

Production of superoxide radical in reductive metabolism of a synthetic food-coloring agent, indigocarmine, and related compounds.

Indigocarmine, which is widely used as a synthetic colouring agent for foods and cosmetics in many countries, was reduced to its leuco form and decolorized by rat liver microsomes with NADPH under anaerobic conditions. The reductase activity was enhanced in liver microsomes of phenobarbital-treated rats, and inhibited by diphenyliodonium chloride, a NADPH-cytochrome P450 reductase (P450 reductase) inhibitor, but was not inhibited by SKF 525-A or carbon monoxide. Indigocarmine reductase activity was exhibited by purified rat P450 reductase. In contrast, when indigocarmine was incubated with rat liver microsomes and NADPH under aerobic conditions, superoxide radical was produced and its production was inhibited by superoxide dismutase and diphenyliodonium chloride. When indigocarmine was incubated with purified rat P450 reductase in the presence of NADPH, superoxide radical production was enhanced 17.7-fold (similar to the enhancement of indigocarmine-reducing ability) as compared with that of rat liver microsomes. A decrease of one molecule of NADPH was accompanied with formation of about two molecules of superoxide radical. P450 reductase exhibited little reductase activity towards indigo and tetrabromoindigo, which also afforded little superoxide radical under aerobic conditions. These results indicate that indigocarmine is reduced by P450 reductase to its leuco form, and superoxide radical is produced by autoxidation of the leuco form, through a mechanism known as futile redox cycling.

Animals↗

PubMed2005

Estrogenic and antiandrogenic activities of 17 benzophenone derivatives used as UV stabilizers and sunscreens.

Estrogenic and antiandrogenic activities of benzophenone and 16 of its derivatives, which are used as UV stabilizers, were comparatively examined with hormone-responsive reporter assay in various cell lines. Hydroxylated benzophenones exhibited estrogenic activity in human breast cancer cell line MCF-7, but their activities varied markedly. The highest activity was observed with 2,4,4'-trihydroxybenzophenone (2.4.4'-triOH-BP), followed by 2,3',4,4'-tetrahydroxybenzophenone, 4,4'-dihydroxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone, 4-hydroxybenzophenone and 2,4-dihydroxybenzophenone. Benzophenone itself showed little activity in the assay. In contrast, benzophenone and some related compounds showed significant inhibitory effects on the androgenic activity of dihydrotestosterone in rat fibroblast cell line NIH3T3. The highest activity was observed with 2,4,4'-triOH-BP, followed by 2,3',4,4'-tetrahydroxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone, 3-hydroxybenzophenone and 2,2'-dihydroxybenzophenone. However, 2,3,4,4'-tetrahydroxybenzophenone and 2,3,4-trihydroxybenzophenone showed little activity. 2,4-Dihydroxybenzophenone, 2,4,4'-triOH-BP and benzophenone gave positive responses in uterotrophic assay using ovariectomized rats, and 2,4,4'-triOH-BP was positive in the Hershberger assay using castrated rats. These results suggest that a 4-hydroxyl group on the phenyl ring of benzophenone derivatives is essential for high hormonal activities, and the presence of other hydroxyl groups markedly alters these activities.

Androgen Antagonists↗

PubMed2005

Neuroprotective effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline on cultured rat mesencephalic neurons in the presence or absence of various neurotoxins.

1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) is an endogenous brain amine and its content in parkinsonian brain is decreased compared with that in control brain. There is some evidence that 1MeTIQ protects dopaminergic neurons against dysfunction such as that seen in Parkinson's disease. In this study, we examined the neuroprotective effect of 1MeTIQ against four dopaminergic neurotoxins, 1-methyl-4-phenylpyridinuim ion, 6-hydroxydopamine, rotenone, and l-benzyl-1,2,3,4-tetrahydroisoquinoline, in cultured rat mesencephalic neurons. 1MeTIQ exerted neuroprotective action against all these toxins. Furthermore, (R)-1MeTIQ was neuroprotective, while (S)-1MeTIQ had little effect, indicating that the effect is stereoselective. The protective action of 1MeTIQ was most effective in mesencephalic neurons, especially in tyrosine hydroxylase-positive neurons. 1MeTIQ showed no affinity for dopamine receptors and did not influence the inhibition of mitochondrial respiratory complex I by rotenone, 1-methyl-4-phenylpyridinuim ion, or 1-benzyl-1,2,3,4-tetrahydroisoquinoline. These results raise the possibility that 1MeTIQ indirectly acts as an anti-oxidant such as the induction of anti-oxidative enzymes, because all these four neurotoxins can burden oxidative stress in common. This is the first report to confirm a protective effect of 1MeTIQ at the cultured neuron level, and it may have potential as a lead compound for the development of new agents to treat Parkinson's disease.

Animals↗

PubMed2005

Comparative study of the endocrine-disrupting activity of bisphenol A and 19 related compounds.

The endocrine-disrupting activities of bisphenol A (BPA) and 19 related compounds were comparatively examined by means of different in vitro and in vivo reporter assays. BPA and some related compounds exhibited estrogenic activity in human breast cancer cell line MCF-7, but there were remarkable differences in activity. Tetrachlorobisphenol A (TCBPA) showed the highest activity, followed by bisphenol B, BPA, and tetramethylbisphenol A (TMBPA); 2,2-bis(4-hydroxyphenyl)-1-propanol, 1,1-bis(4-hydroxyphenyl)propionic acid and 2,2-diphenylpropane showed little or no activity. Anti-estrogenic activity against 17beta-estradiol was observed with TMBPA and tetrabromobisphenol A (TBBPA). TCBPA, TBBPA, and BPA gave positive responses in the in vivo uterotrophic assay using ovariectomized mice. In contrast, BPA and some related compounds showed significant inhibitory effects on the androgenic activity of 5alpha-dihydrotestosterone in mouse fibroblast cell line NIH3T3. TMBPA showed the highest antagonistic activity, followed by bisphenol AF, bisphenol AD, bisphenol B, and BPA. However, TBBPA, TCBPA, and 2,2-diphenylpropane were inactive. TBBPA, TCBPA, TMBPA, and 3,3'-dimethylbisphenol A exhibited significant thyroid hormonal activity towards rat pituitary cell line GH3, which releases growth hormone in a thyroid hormone-dependent manner. However, BPA and other derivatives did not show such activity. The results suggest that the 4-hydroxyl group of the A-phenyl ring and the B-phenyl ring of BPA derivatives are required for these hormonal activities, and substituents at the 3,5-positions of the phenyl rings and the bridging alkyl moiety markedly influence the activities.

Air Pollutants, Occupational↗

PubMed2005

A new class of androgen receptor antagonists bearing carborane in place of a steroidal skeleton.

A new class of androgen receptor antagonists containing dicarba-closo-dodecaborane (carborane) as a hydrophobic skeletal structure is described. The designed molecules bear the characteristic polar components of endogenous agonists, but have a hydrophobic carborane cage instead of the steroidal skeleton. These compounds bind to androgen receptor and show anti-androgenic activity towards androgen-dependent SC-3 cells with almost the same potency as the known anti-androgen hydroxyflutamide.

Androgen Antagonists↗

PubMed2005

Purification and characterization of rat liver enzyme catalyzing stereoselective reduction of acetylpyridines.

Acetylpyridines (1-3) are known as aroma components of foods, perfumes, and smoking suppressants, showing several biological activities and constituting part of the structure of some important biologically active compounds. We purified and characterized an enzyme that catalyzes the stereoselective reduction of acetylpyridines so that we could clarify its function. The enzyme participating in the reductive metabolism of 4-acetylpyridine (1) in the rat liver was purified by successively applying ammonium sulfate fractionation, anion-exchange, gel filtration, and affinity chromatography, and it was definitively identified as 3alpha-HSD. It preferentially reduced acetylpyridines (1-3) and acetophenone (7) to their corresponding (S)-alcohols, with high enantioselectivity. Kinetic analyses of the compounds were performed, and the V(max)/K(m) values decreased in the order of 4-, 2-, and 3-acetylpyridine (1, 3, 2), while acetophenone (7) showed almost the same value as 3-acetylpyridine (2). These results suggested that the reduction of the substrates by 3alpha-HSD is affected by the nitrogen atom in the aromatic ring.

3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)↗

PubMed2005

Preparative monohydroxyflavanone syntheses and a protocol for gas chromatography-mass spectrometry analysis of monohydroxyflavanones.

We describe a facile efficient, and preparative approach for monohydroxyflavanone syntheses. Using this protocol, a hydroxyl is regio-selectively introduced at one carbon of a flavanone A- or B-ring per synthesis. The seven possible isomers were each synthesized from the corresponding monomethoxymethoxylated 2'-hydroxychalcones in acidic solution. These monohydroxyflavanones were characterized using a gas chromatography-mass spectrometry (GC-MS) system that incorporated a DB-5 capillary column. Ours is the first report of a preparative synthetic method during which a single hydroxyl can be selectively added to a flavanone A- or B-ring at any position. We are also the first to develop a procedure that separates the seven isomers by GC and characterizes the mass spectra of the isomers. Both the synthetic method and the GC-MS conditions may become important tools during future flavanone metabolism and oxidation studies.

Flavanones↗

PubMed2005

[Study of Parkinson's disease-causing mechanism and development of anti-Parkinson's disease drugs using endogenous substances in brain].

There have been many reports showing 1,2,3,4-tetrahydroisoquinoline(TIQ) derivatives may be related to the onset of Parkinson's disease. 1-Benzyl-1,2,3,4-tetrahydroisoquinoline(1BnTIQ) was detected as a novel endogenous amine in mouse brain and parkinsonian CSF. The level of 1BnTIQ was very high in CSF of some parkinsonian patients compared with that of controls with other neurological diseases. Repeated administration of 1BnTIQ induced behavior abnormalities. We suggest that 1BnTIQ may be related to the idiopathic Parkinson's disease. On the other hand, 1-methyl TIQ (1MeTIQ), an endogenous amine in the brain, prevented 1BnTIQ-induced parkinsonism in mice. So 1MeTIQ is a candidate for anti-parkinsonian drugs.

Animals↗

PubMed2004

Anti-thyroid hormonal activity of tetrabromobisphenol A, a flame retardant, and related compounds: Affinity to the mammalian thyroid hormone receptor, and effect on tadpole metamorphosis.

The thyroid hormone-disrupting activity of tetrabromobisphenol A (TBBPA), a flame retardant, and related compounds was examined. TBBPA, tetrachlorobisphenol A (TCBPA), tetramethylbisphenol A (TMBPA) and 3,3'-dimethylbisphenol A (DMBPA) markedly inhibited the binding of triiodothyronine (T3; 1 x 10(-10) M) to thyroid hormone receptor in the concentration range of 1 x 10(-7)-1 x 10(-4) M, while bisphenol A and 2,2-diphenylpropane were inactive. TBBPA, TCBPA, TMBPA and DMBPA did not exhibit thyroid hormonal activity in a thyroid hormone-responsive reporter assay using a Chinese hamster ovary cell line (CHO-K1) transfected with thyroid hormone receptor alpha1 or beta1, but TBBPA and TCBPA showed significant anti-thyroid hormone effects on the activity of T3 (1 x 10(-8) M) in the concentration range of 3 x 10(-6) - 5 x 10(-5) M. The thyroid hormone-disrupting activity of TBBPA was also examined in terms of the effect on amphibian metamorphosis stimulated by thyroid hormone. TBBPA in the concentration range of 1 x 10(-8) to 1 x 10(-6) M showed suppressive action on T3 (5 x 10(-8) M)-enhancement of Rana rugosa tadpole tail shortening. These facts suggest that TBBPA, TCBPA, TMBPA and DMBPA can act as thyroid hormone-disrupting agents.

Animals↗

PubMed2004

Inhibitory effect of organotin compounds on rat neuronal nitric oxide synthase through interaction with calmodulin.

Organotin compounds, triphenyltin (TPT), tributyltin, dibutyltin, and monobutyltin (MBT), showed potent inhibitory effects on both L-arginine oxidation to nitric oxide and L-citrulline, and cytochrome c reduction catalyzed by recombinant rat neuronal nitric oxide synthase (nNOS). The two inhibitory effects were almost parallel. MBT and TPT showed the highest inhibitory effects, followed by tributyltin and dibutyltin; TPT and MBT showed inhibition constant (IC(50)) values of around 10microM. Cytochrome c reduction activity was markedly decreased by removal of calmodulin (CaM) from the complete mixture, and the decrease was similar to the extent of inhibition by TPT and MBT. The inhibitory effect of MBT on the cytochrome c reducing activity was rapidly attenuated upon dilution of the inhibitor, and addition of a high concentration of CaM reactivated the cytochrome c reduction activity inhibited by MBT. However, other cofactors such as FAD, FMN or tetrahydrobiopterin had no such ability. The inhibitory effect of organotin compounds (100microM) on L-arginine oxidation of nNOS almost vanished when the amount of CaM was sufficiently increased (150-300microM). It was confirmed by CaM-agarose column chromatography that the dissociation of nNOS-CaM complex was induced by organotin compounds. These results indicate that organotin compounds disturb the interaction between CaM and nNOS, thereby inhibiting electron transfer from the reductase domain to cytochrome c and the oxygenase domain.

Amino Acid Oxidoreductases↗

PubMed2004

Infant acute lymphoblastic leukemia with MLL gene rearrangements: outcome following intensive chemotherapy and hematopoietic stem cell transplantation.

Forty-four infants with acute lymphoblastic leukemia (ALL) characterized by MLL gene rearrangements were treated on a protocol of intensive chemotherapy followed by hematopoietic stem cell transplantation (HSCT) between November 1998 and June 2002. The remission induction rate was 91.0%, and the 3-year overall survival and event-free survival (EFS) rates, with 95% confidence intervals, were 58.2% (43.5%-72.9%) and 43.6% (28.5%-58.7%), respectively. Univariate analysis of EFS by presenting features indicated a poorer outcome in patients younger than 6 months of age with high white blood cell counts (>/= 100 x 10(9)/L; EFS rate, 9.4% versus 55.1% for all others, P = .0036) and in those with central nervous system invasion (EFS rate, 10.0% versus 56.9% for all others, P = .0073). The 3-year posttransplantation EFS rate for the 29 patients who underwent HSCT in first remission was 64.4% (46.4%-82.4%). In this subgroup, only the timing of HSCT (first remission versus others) was a significant risk factor by multivariate analysis (P < .0001). These results suggest that early introduction of HSCT, possibly with a less toxic conditioning regimen, may improve the prognosis for infants with MLL(+) ALL. Identification of subgroups or patients who respond well to intensified chemotherapy alone should have a high priority in future investigations.

Age Factors↗

PubMed2004

Detection and determination of reticuline and N-methylcoculaurine in the Annonaceae family using liquid chromatography-tandem mass spectrometry.

In Guadeloupe, the French West Indies, there is a high incidence of atypical parkinsonism or progressive supranuclear palsy, and all of the investigated patients had taken herbal tea or tropical fruits of the Annonaceae family. Local inhabitants consume the fruits, and also drink tea made from the leaves. In the present study, we used liquid chromatography-tandem mass spectrometry (LC/MS/MS) with multiple reaction monitoring (MRM) to detect low-molecular-weight neurotoxic benzylisoquinoline derivatives in the Annonaceae family. We detected reticuline and N-methylcoculaurine in every Annona muricata sample examined, except for pulp and seed. They were not detected in sweetsop fruits. Norreticuline was not detected in any sample. These three compounds were toxic to SH-SY5Y neuroblastoma cells and inhibited mitochondrial respiratory complex I. It is possible that uptake of the benzylisoquinoline derivatives reticuline and N-methylcoculaurine and their accumulation in the brain may be related to the pathogenesis of the local endemic disease.

Alkaloids↗

PubMed2004

Aryl hydrocarbon receptor-mediated induction of microsomal drug-metabolizing enzyme activity by indirubin and indigo.

Indirubin and indigo, which are thought to be natural ligands for aryl hydrocarbon receptor (AhR), showed marked AhR ligand activities in a reporter gene assay using recombinant yeast. Their activities were comparable with or more potent than that of 2,3,7,8-tetrachlorodibenzo-p-dioxin. When indirubin and indigo were administered to mice, ethoxyresorufin-O-dealkylase and methoxyresorufin-O-dealkylase activities in the liver were increased, but subsequently decreased within 2 days. Indirubin was more potent than indigo. Levels of cytochrome P450 1A1/2 proteins and mRNAs in the liver of mice dosed with indirubin were also enhanced. These enhancing effects of indirubin and indigo were not observed in AhR knock-out mice. Ethoxyresorufin-O-dealkylase and methoxyresorufin-O-dealkylase activities in rat hepatocytes and HepG2 cells were enhanced by the addition of indirubin or indigo, but less potently than by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Indigocarmine, a sulfate derivative of indigo, which is used as food additive, did not show these inducing effects on drug-metabolizing enzymes. Our results suggest that indirubin and indigo act as inducers for cytochrome P450 1A1/2 mediated by AhR in mammals in vivo.

Animals↗

PubMed2004

Geographic variability in expression of the sex-linked AAT-1 gene of the bell-ring frog, Buergeria buergeri.

Cytological observation and artificial crossing experiments were used to examine the geographic differences in the sex-determining mechanism and mode of inheritance of the sex-linked AAT-1 gene in the bell-ring frog, Buergeria buergeri. The AAT-1 phenotypes were also examined by allozyme analysis using field-caught females and males collected from 19 populations from the Honshu, Shikoku, and Kyushu islands of Japan, in order to comprehensively elucidate the geographic variability in the expression of the sex-linked AAT-1 gene of B. buergeri. The results showed that the Aomori population of B. buergeri from the northern end of Honshu was female heterogametic in sex determination, that chromosome No. VII was a sex chromosome of the ZZ/ZW type, and that the sex-linked AAT-1 gene was expressed on both the Z and W chromosomes. This mode of AAT-1 expression in the Aomori population was different from that in the Hiroshima population from western Honshu, in which the AAT-1 gene was expressed on the Z chromosome but not on the W chromosome. The results also showed that there was no differentiation among populations in the expression of the AAT-1 genes on the Z chromosome, whereas two populations, the Hiroshima and Aomori frogs, exhibited distinct modes of expression of the AAT-1 gene on the W chromosome. These two modes of expression may be widely distributed in western and eastern Japan, and coexist in the central part of Honshu.

Animals↗