Sex differences in gallbladder bile acid composition and hepatic steroid 12 alpha-hydroxylase activity in hamsters

The gallbladder bile acid composition and the activity of the hepatic steroid 12 alpha-hydroxylase were determined in male and female hamsters. Cholic acid, chenodeoxycholic acid, and deoxycholic acid were the major bile acids in both sexes; in addition, 7-ketodeoxycholic acid and lithocholic acid were present. A sex-linked difference in the ratio of cholic acid (plus its metabolites) to chenodeoxycholic acid (plus its metabolite) was observed. The ratio was 1.93 +/- 0.39 in males and 2.74 +/- 0.54 in females. Another sex-linked difference was found in the activity of the 12 alpha-hydroxylase. The extent of the 12 alpha-hydroxylation of 7 alpha-hydroxycholest-4-en-3-one to yield 7 alpha, 12 alpha-dihydroxycholest-4-en-3-one was about two times greater in the microsomal suspension obtained from the liver of female hamsters than in that of male hamsters. A positive correlation between the 12 alpha-hydroxylase activity and the ratio of cholic acid/chenodeoxycholic acid was also observed. These results strongly support the proposal that the activity of the 12 alpha-hydroxylase is the major factor in determining the relative proportion of cholic acid and chenodeoxycholic acid formed from cholesterol in the liver.     

Characterization of the bile acid profile in developing male and female hamsters in response to dietary cholesterol challenge

The Syrian golden hamster is a frequently used model to study cholesterol and bile acid metabolism as well as cholesterol-induced cholelithiasis. However, diet-induced gallstones seem limited to young male hamsters of certain strains that develop depressed cholate/chenodeoxycholate bile acid ratios. To further elucidate gender and age specific aspects of cholesterol and bile acid metabolism, i.e. a possible age-related bile acid/gallstone relationship, plasma and biliary lipids and bile acid composition were analyzed in male and female hamsters under various physiological conditions of age and diet, the latter formulated with and without dietary cholesterol. During normal development (no cholesterol challenge) the percentage of cholic acid decreased while chenodeoxycholate increased, the shift being more pronounced in males. Furthermore, female hamsters had higher total plasma cholesterol than in males, while hepatic and biliary lipids did not differ. When challenged with excessive dietary cholesterol, female hamsters again developed significantly higher total plasma and hepatic cholesterol concentrations. Biliary lipids and cholesterol gallstone incidence revealed a significant gender effect with male hamsters developing a higher lithogenic index and more gallstones (cholesterol and pigment stones) than females. Female hamsters revealed a lower percentage of chenodeoxycholate and a higher percentage of cholate resulting in a more protective, higher cholate/cheno ratio (1.5 +/- 1.0) than in males (1.0 +/- 0.2). In summary, the bile acid pattern in developing and cholesterol-fed hamsters renders females less susceptible to gallstones, in part because they maintain more favorable biliary lipid and bile acid profiles, characterized by lower molar percentages of biliary cholesterol and chenodeoxycholate.     

Bioactivation of 7-hydroxymethyl-12- methyibenz[a]anthracene by rat liver bile acid sulfotransferase I

The bioactivation of 7-hydroxy-methyl-12-methylbenz[a]anthracene (HMBA) to an electrophilic sulfuric acid ester metabolite has been shown to be catalyzed by rat liver bile acid sulfotransferase I (BAST I). The sulfation and activation of HMBA by BAST I was determined by the ability of sulfated HMBA to form DNA ad-ducts. The BAST I was also shown to react with rabbit anti-human dehydroepiandrosterone sulfotransferase antisera and to represent a major form of hydroxysteroid/bile acid sulfotransferase in female rat liver cytosol. Higher levels of BAST I activity and immunoreactivity as well as HMBA-DNA adduct formation were detected in female rat liver cytosol than in male rat liver cytosol. The bioactivation of HMBA by pure BAST I was dependent on the presence of 3′-phosphoadenosine 5′-phos-phosulfate (PAPS) in the reaction and was inhibited by dehydroepiandrosterone, a physiological substrate for BAST I. Glutathione, a cellular nucleophile with important protective properties, decreased DNA adduct formation in the HMBA sulfation reaction in the absence of glutathione S-transferase activity. These results indicate the usefulness of BAST I to investigate the sulfation and activation of HMBA and probably other hydroxy-methylated polyaromatic hydrocarbons to electrophilic and mutagenic metabolites under defined reaction conditions.     

Cloning, expression, and regulation of lithocholic acid 6 beta-hydroxylase.

We have isolated a hamster liver cDNA whose expression is induced upon feeding hamsters with a cholic acid-rich diet. It was identified as a cytochrome P450 family 3 protein, by sequence homology, and named CYP3A10. The activity of CYP3A10 was determined by transient expression of its cDNA in transfected COS cells and was found to hydroxylate lithocholic acid at position 6 beta. CYP3A10 RNA is 50-fold higher in males than in female hamsters. In males, it appears to be regulated by age with expression highest after puberty. Shortly after weaning (28 days), cholic acid feeding of male hamsters elevates the level of message over that of hamsters fed with normal laboratory chow. Females do not exhibit regulation by cholic acid. In hamster liver, murideoxycholic acid, the 6 beta-metabolite of lithocholic acid, is the major hydroxylated product of lithocholic acid. Lithocholic acid 6 beta-hydroxylase (6 beta-hydroxylase) activity is greatly diminished in hamster female liver microsomes as would be expected due to the lack of CYP3A10 mRNA in females. Additionally, male liver microsomal 6 beta-hydroxylase activity was increased by cholic acid feeding, consistent with the cholic acid-mediated induction of its RNA. These results indicate that, in male hamsters, 6 beta-hydroxylation is the major pathway for detoxification of lithocholate and that, likely, CYP3A10 is responsible for that activity.     

Sex-linked differences in bile acid metabolism of germfree rats

The bile acid composition was investigated in male and female germfree rats. β-Muricholic acid and cholic acid were the major bile acids in both sexes; in addition, 3β-hydroxy-5-cholenoic acid, chenodeoxycholic acid, α-muricholic acid, allochenodeoxycholic acid and allocholic acid were present. Important sex-linked differences in the relative amounts and the sulfation of these substances were observed. β-Muricholic and cholic acid accounted for 61.4 % and 27.7 % of total bile acids in the small intestine of males; females had 38.9 % of β-muricholic acid and 50 % of cholic acid. In females, the bile acid sulfate fraction increased from 1.1 % in the small intestine to 22.3 % in the large intestine; in males these values were 0.2 % and 1.7 %, respectively. A considerable increase in the relative amounts of allochenodeoxycholic and allocholic acid was observed in the cecum and large intestine of the female rat, where more than 70 % of these substances was in the bile acid sulfate fraction. In males these allo-bile acids were mainly in the unsulfated fraction and their relative amounts did not increase in the large intestine.     

Mercury inhibition of avian fatty acid synthetase complex.

(1) Subcutaneous or intra-abdominal injections of 8 mg of HgCl2/100 g body weight markedly depressed hepatic fatty acid synthetase activity of chicks at 1 h post-injection. The depression occurred despite the fact that the chicks continued to eat up until the time they were killed. Under these same conditions, the hepatic activity of acetyl-CoA carboxylase (EC 6.4.1.2) was not affected by HgCl2, while the activity of the mitochondrial system of fatty acid elongation was stimulated. (2) When 2-mercaptoethanol was included in the incubation medium for a highly purified preparation of fatty acid synthetase, 500 muM HgCl2 was required to show definite inhibition of the enzyme. When 2-mercaptoethanol was omitted, 50 muM HgCl2 was inhibitory and 100 muM HgCl2 abolished enzyme activity. (3) 2 mM dithiothreitol completely protected the purified fatty acid synthetase preparation from inhibition by 100 muM HgCl2. When dithiothreitol was added after the addition of enzyme to the mercury-containing medium, protection of the enzyme was not complete. (4) Dialysis of cytosol fractions from chicks injected with HgCl2 against 500 vol. of 0.2 M potassium phosphate buffer (pH 7.0) containing 1 mM EDTA and 10 mM dithiothreitol for 4 h at 4 degrees stimulated the fatty acid synthetase activity of the fractions. Dialysis of cytosol fractions from noninjected chicks under the same conditions was without effect on fatty acid synthetase activity. (5) These data support the hypothesis that the inhibitory effect of HgCl2 administered in vivo on hepatic fatty acid synthetase activity in chicks is mediated through the interaction of mercury with the sulfhydryl groups of the enzyme.     

Cholesterol, bile acid, and lipoprotein metabolism in two strains of hamster, one resistant, the other sensitive (LPN) to sucrose-induced cholelithiasis

A comprehensive study of cholesterol, bile acid, and lipoprotein metabolism was undertaken in two strains of hamster that differed markedly in their response to a sucrose-rich/low fat diet. Under basal conditions, hamsters from the LPN strain differed from Janvier hamsters by a lower cholesterolemia, a higher postprandial insulinemia, a more active cholesterogenesis in both liver [3- to 4-fold higher 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMG-CoAR) activity and mRNA] and small intestine, and a lower hepatic acyl-coenzyme A:cholesterol acyltransferase activity. Cholesterol saturation indices in the gallbladder bile were similar for both strains, but the lipid concentration was 2-fold higher in LPN than in Janvier hamsters. LPN hamsters had a lower capacity to transform cholesterol into bile acids, shown by the smaller fraction of endogenous cholesterol converted into bile acids prior to fecal excretion (0.34 vs. 0.77). In LPN hamsters, the activities of cholesterol 7alpha-hydroxylase (C7OHase) and sterol 27-hydroxylase (S27OHase), the two rate-limiting enzymes of bile acid synthesis, were disproportionably lower (by 2-fold) to that of HMG-CoAR. When fed a sucrose-rich diet, plasma lipids increased, dietary cholesterol absorption improved, hepatic activities of HMG-CoA reductase, C7Ohase, and S27OHase were reduced, and intestinal S27OHase was inhibited in both strains. Despite a similar increase in the biliary hydrophobicity index due to the bile acid enrichment in chenodeoxycholic acid and derivatives, only LPN hamsters had an increased lithogenic index and developed cholesterol gallstones (75% incidence), whereas Janvier hamsters formed pigment gallstones (79% incidence).These studies indicate that LPN hamsters have a genetic predisposition to sucrose-induced cholesterol gallstone formation related to differences in cholesterol and bile acid metabolism.     

Modulation of cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase activities by steroids and physiological conditions in hamster.

Our purpose was to examine the in vitro modulation of liver mitochondrial sterol 27-hydroxylase (S27OHase) and microsomal cholesterol 7alpha-hydroxylase (CH7alphaOHase) activities by certain drugs, sterols, oxysterols and bile acids, and to compare the influence of sex, age, diet and cholestyramine on these activities, in the hamster. In vitro, 7beta-hydroxycholesterol and 5alpha-cholestan-3beta-ol (cholestanol) were strong inhibitors (at 2 microM) of both enzyme activities, while 5beta-cholestan-3alpha-ol (epicoprostanol, 2 microM) and cyclosporin A (20 microM) inhibited S27OHase, but not CH7alphaOHase. These data suggest that a hydroxyl group at the 7alpha position is not required to inhibit CH7alphaOHase and that the presence of an aliphatic CH2-CH-(CH3)2 chain appears to be structurally important for S27OHase activity. Both enzyme activities remained unchanged by hyodeoxycholic acid (40 or 80 microM) while epicoprostanol inhibited only S27OHase and chenodeoxycholic acid only CH7alphaOHase. Adult (9-week old) male or female hamsters displayed similar S27OHase activity but the CH7alphaOHase activity was lower in females than in males, suggesting that the neutral bile acid pathway has a less important role in females. In male hamsters, S27OHase activity did not change with age, while CH7alphaOHase activity significantly increased (one-year vs 9-week old). A semi-purified sucrose-rich (lithogenic) diet significantly lowered both enzyme activities compared to the commercial diet. Cholestyramine induced a stimulation of both enzymes, slightly more vigorously however for the key enzyme involved in the neutral pathway. Taken together, these data indicate that the two enzymes are separately regulated and that certain drugs or steroid compounds can be useful for specifically inhibiting or stimulating the neutral or acidic bile acid pathway.     

Steroid metabolism in the cat. Biliary and urinary excretion of metabolites of [4-14C]oestradiol

1. [4-¹⁴C]Oestradiol was administered to seven male, seven female and two castrated male cats as a single intravenous injection. Bile and urine were collected for 6h. 2. The radioactivity was excreted mainly in the bile of all animals (53–60%); only approx. 1% of the dose appeared in the urine. 3. Bile and urine samples were hydrolysed successively by β-glucuronidase, cold acid and hot acid. There were significant differences (P<0.005) between the percentage of the dose present in the bile fractions hydrolysed by β-glucuronidase (male, 9.0±1.7%; female, 18.6±1.45%) and by cold acid (male, 18.9±1.44%; female 12.1±1.02%). The excretion of radioactivity in these fractions by the castrated male cats was closer to that of female cats. 4. Approx. 20–27% of the dose could not be extracted from aqueous solution (pH10.5) by ethyl acetate–ether after hydrolysis.     

A comparative study of the sulfation of bile acids and a bile alcohol by the Zebra danio (Danio rerio) and human cytosolic sulfotransferases (SULTs)

The current study was designed to examine the sulfation of bile acids and bile alcohols by the Zebra danio (Danio rerio) SULTs in comparison with human SULTs. A systematic analysis using the fifteen Zebra danio SULTs revealed that SULT3 ST2 and SULT3 ST3 were the major bile acid/alcohol-sulfating SULTs. Among the eleven human SULTs, only SULT2A1 was found to be capable of sulfating bile acids and bile alcohols. To further investigate the sulfation of bile acids and bile alcohols by the two Zebra danio SULT3 STs and the human SULT2A1, pH-dependence and kinetics of the sulfation of bile acids/alcohols were analyzed. pH-dependence experiments showed that the mechanisms underlying substrate recognition for the sulfation of lithocholic acid (a bile acid) and 5α-petromyzonol (a bile alcohol) differed between the human SULT2A1 and the Zebra danio SULT3 ST2 and ST3. Kinetic analysis indicated that both the two Zebra danio SULT3 STs preferred petromyzonol as substrate compared to bile acids. In contrast, the human SULT2A1 was more catalytically efficient toward lithocholic acid than petromyzonol. Collectively, the results imply that the Zebra danio and human SULTs have evolved to serve for the sulfation of, respectively, bile alcohols and bile acids, matching the cholanoid profile in these two vertebrate species.     

Investigations on the sodium dependence of bile acid fluxes in the isolated perfused rat liver.

At [Na+]o = 118 mM the concentrative transfer of cholic and taurocholic acid from the perfusate into the isolated rat liver displays saturation kinetics (taurocholate: V = 299 nmol-min-1-g-1, Km = 61 muM; Cholate: V=327 nmol-min-1-g-1, Km = 436 muM). Perfusion with an isotonic sodium-free medium did not change the feature of a carrier-mediated transport but did markedly reduce V without affecting Km (taurocholate: V = 65 nmol-min-1-g-1, Km = 78 muM; cholate: V = 104 nmol-min-1-g-1, Km = 354 muM). It was experimentally assured that the observed reduction of bile salt uptake was not a consequence of regurgitation of bile salts or due to an excessive intracellular accumulation during cholestasis in the sodium-free state. The rate of taurocholate efflux is very low when compared with the rapid rate of the uptake. A stimulatory action of extracellular sodium on this pathway was also observed. Inhibition of the (Na+ + K+)-ATPase by 1 mM ouabain resulted in a decrease of bile salt uptake. Activation of the enzyme by potassium readmission to a K+-deprived liver enhanced bile salt uptake. The immediate response to alteration of the enzyme activity suggests a close association of a fraction of bile acid active transport with the sodium pump.     

Taurine increases bile acid pool size and reduces bile saturation index in the hamster

There is evidence that increased availability of taurine enhances the proportion of taurine-conjugated bile acids in bile. To explore the possibility that taurine treatment could also influence hepatic cholesterol and bile acid metabolism, we fed female hamsters for 1 week and measured both the biliary lipid content and the microsomal level of the rate-limiting enzymes of cholesterol and bile acid synthesis. In these animals the cholesterol 7 alpha-hydroxylase activity was significantly greater in respect to controls (P less than 0.05). The total HMG-CoA reductase activity, as well as that of the active form, was similarly increased. The stimulation of 7 alpha-hydroxycholesterol synthesis was associated with an expansion of the bile acid pool size in taurine-fed animals. Taurine feeding was observed to induce an increase in bile flow as well as in the rate of excretion of bile acids, whereas the secretion rate of cholesterol in bile was decreased. As a consequence, the saturation index was significantly lower in taurine-fed animals (P less than 0.05). The possible mechanisms through which taurine exhibits the modification of the enzyme activities and of the biliary lipid composition are discussed.     

Male priming pheromone is present in bile, as well as urine, of female rainbow trout

The bile of sexually mature female rainbow trout Oncorhynchus mykiss has pheromonal activity which causes a significant increase in concentrations of 17,20β-dihydroxy-4-pregnen-3-one in the plasma of males. Bile from male trout is inactive. The activity in the female bile binds to octadecylsilane and can be eluted with methanol. The synthetic bile acids, taurocholic acid and taurolithocholic acid, are inactive.     

Selective inhibition of CYP27A1 and of chenodeoxycholic acid synthesis in cholestatic hamster liver

The aim of this study was to explore the regulation of serum cholic acid (CA)/chenodeoxycholic acid (CDCA) ratio in cholestatic hamster induced by ligation of the common bile duct for 48 h. The serum concentration of total bile acids and CA/CDCA ratio were significantly elevated, and the serum proportion of unconjugated bile acids to total bile acids was reduced in the cholestatic hamster similar to that in patients with obstructive jaundice. The hepatic CA/CDCA ratio increased from 3.6 to 11.0 (P<0.05) along with a 2.9-fold elevation in CA concentration (P<0.05) while the CDCA level remained unchanged. The hepatic mRNA and protein level as well as microsomal activity of the cholesterol 7alpha-hydroxylase, 7alpha-hydroxy-4-cholesten-3-one 12alpha-hydroxylase and 5beta-cholestane-3alpha,7alpha,12alpha-triol 25-hydroxylase were not significantly affected in cholestatic hamsters. In contrast, the mitochondrial activity and enzyme mass of the sterol 27-hydroxylase were significantly reduced, while its mRNA levels remained normal in bile duct-ligated hamster. In conclusion, bile acid biosynthetic pathway via mitochondrial sterol 27-hydroxylase was preferentially inhibited in bile duct-ligated hamsters. The suppression of CYP27A1 is, at least in part, responsible for the relative decreased production of CDCA and increased CA/CDCA ratio in the liver, bile and serum of cholestatic hamsters.     

Induction of P-450 isoenzyme activities in Syrian golden hamster liver compared to rat liver as probed by the rate of 7-alkoxyresorufin-O-dealkylation

The activities of 7-ethoxyresorufin-O-deethylase (EROD), 7-pentoxyresorufin-O-deethylase (PROD), 7-ethoxycoumarin-O-deethylase (ECOD) and aromatic hydrocarbon hydroxylase (AHH) were measured in hepatic microsomes from male and female Wistar rats and Syrian golden hamsters in order to probe the basal activity and the inducibility by phenobarbital (PB) and 3-methylcholanthrene (MC) of different P-450 isoenzymes. The basal activities of EROD and ECOD, but not PROD and AHH, were higher in male hamsters than in male rats. No sex-related difference in enzyme activities was observed with hamsters, whereas male rats had a higher ECOD and AHH activity than female rats. Induction by PB led to a 450-fold and 250-fold increase in PROD activity in male and female rat liver microsomes, respectively, while MC had a more pronounced inductive effect on EROD activity in this species. In hamsters, EROD activity was induced by MC but not by PB. Unexpectedly PROD activity in male and female hamster liver microsomes was only moderately induced by PB, the extent being lower than on induction by MC. Therefore, the activity of PROD, which is useful as a specific enzymatic assay for P-450 IIB in the rat liver, cannot be used to probe PB-like inducers in the hamster liver.     

Melatonin in the lacrimal gland: first demonstration and experimental manipulation

NAT, HIOMT and melatonin are described in the extra-orbital lacrimal glands. The extra-orbital lacrimal glands of female Syrian hamsters contain higher NAT activity and melatonin levels than those in male glands, while male glands have higher HIOMT activity. Castration did not change melatonin in the lacrimal glands, although NAT and HIOMT activities were altered. The exposure of female hamsters to light in the morning (0600h) was associated with a reduction in both NAT activity and melatonin levels. Porphyrins were not detected in the lacrimal glands of either male or female hamsters.     

Occurrence of sulfated 5alpha-cholanoates in rat bile

Bile acids in bile from male and female rats with cannulated bile ducts have been analyzed by repetitive scanning gas-liquid chromatography-mass spectrometry after initial fractionation of conjugate classes on diethylaminohydroxypropyl Sephadex LH-20. Sex differences were observed in the amounts and types of bile acids in the sulfate fraction. The proportion of total bile acids excreted as sulfates was higher in female (0.9-1.3%) than in male (0.1-0.2%) rats. Most of the sulfated bile acids had a 5alpha configuration, allochenodeoxycholic acid being the major compound in bile from female rats. This bile acid was also present in the nonsulfate fraction but could not be found in bile from male rats. The results indicate that gas-liquid chromatography-mass spectrometry has to be used to provide sufficient specificity in the bile acid analyses. Thus, compounds from the sulfate fraction having the retention times of cholic and chenodeoxycholic acid derivatives were found to be due to derivatives of the 3beta,5alpha-isomers of these bile acids.     

Gender difference in enzymes related with alcohol consumption in hamster,an avid consumer of alcohol

Syrian golden hamster (Mesocricetus auratus) is extraordinary among laboratory rodents in its ability to drink alcohol. After being given a free choice between 15% ethanol and water for 5 days, both male and female hamsters derived at least 85% of the fluid intake from the ethanol solution. Analysis of the alcohol-metabolizing enzymes in alcohol-na??ve hamsters showed that the male had a higher activity of 57%, 58% and 34% in stomach alcohol dehydrogenase, liver cytochrome P450 1A2 and liver aldehyde dehydrogenase, respectively, compared with the female. The activity of lung angiotensin-converting enzyme, which influence fluid intake, was twofold higher in the male. After 4 weeks of ethanol consumption, the activities of the hepatic alcohol-metabolizing enzymes remained unchanged except cytochrome P450 2E1 which increased 42% and 88% in male and female hamsters, respectively. A reduction of ～80% in the activity of cytochrome P450 1A2 was observed in both genders. The activities of several other cytochrome P450 enzymes were also decreased. Although ethanol consumption did not increase plasma aminotransferase levels, it caused a significant increase in liver weight in female, but not male hamsters.     

Gender differences and time course of castration-induced changes in porphyrins, indoles, and proteins in the Harderian glands of the Syrian hamster.

Sexual differences and the effects of orchidectomy were determined for porphyrin and melatonin concentrations and for the activities of the enzymes N-acetyltransferase and hydroxyindole-O-methyltransferase, which synthesize melatonin from serotonin, in the Harderian glands of the Syrian hamster. Porphyrin concentrations in intact males were about 1/400th those of intact females. Castration for 1 week increased male Harderian porphyrin concentrations 10-fold; by 3 weeks, castrated male porphyrin levels were 140 times those of control values. N-Acetyltransferase activity in intact male Harderian glands was about 4 times that of females. Castration led to a drop in N-acetyltransferase activity to female levels within 2 weeks. Hydroxyindole-O-methyltransferase activity was 7 times higher in females than in males and castration had no effect on male Harderian hydroxyindole-O-methyltransferase activity. Neither gender nor castration influenced Harderian melatonin concentrations. Soluble proteins in Harderian glands from male and female hamsters and from male hamsters castrated for 1 and 4 weeks were examined by sodium dodecyl sulfate--polyacrylamide gel electrophoresis. The gel profiles revealed several differences among the protein distribution in male and female gland lysates. Orchidectomy led to a female protein pattern within 4 weeks.     

Asymmetric learning to avoid heterospecific males in Mesocricetus hamsters

If a female mates with a male of a closely related species, her fitness is likely to decline. Consequently, females may develop behavioral mechanisms to avoid mating with heterospecific males. In some species, one such mechanism is for adult females to learn to discriminate against heterospecific males after exposure to such males. We have previously shown that adult, female Syrian hamsters (Mesocricetus auratus) learn to discriminate against male Turkish hamsters (Mesocricetus brandti) after exposure to a single heterospecific male during 8 days across a wire-mesh barrier. Here we repeated that experiment but this time we exposed female Turkish hamsters to a male Syrian hamster for 8 days and then measured sexual and aggressive behaviors towards that heterospecific male and towards a conspecific male. In contrast to female Syrian hamsters, female Turkish hamsters did not differ in their latency to go into lordosis or in any measure of aggression towards either type of male. Female Turkish hamsters spent less time in lordosis with the heterospecific male, but the percentage of trials in which females copulated with conspecific and heterospecific males did not differ. When comparing females from both species that had been exposed to a heterospecific male for 8days, female Syrian hamsters copulated less and were more aggressive towards the heterospecific male compared to the behavior of female Turkish hamsters. We discuss how this asymmetric response between females of the two species may be due to the much larger geographical range of Turkish hamsters compared to Syrian hamsters.