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PubMed1997

Gender differences in the comparison of self-reported disability and performance measures.

BACKGROUND: Gender differences in functioning among older adults have been well documented. Differential reporting of functional problems by men and women may contribute to this observed difference. The purpose of this study was to examine the gender differences in functional ability by comparing self-reported function to observed performance of physical tasks. METHODS: In 1988, 1,458 men and women ages 71 and older from the New Haven site of the Established Populations for the Epidemiologic Study of the Elderly (EPESE) self-reported activities of daily living (ADL) disability and functional limitations. Subjects' ability to perform 7 tasks was observed. Gender differentials in "accurate" and "inaccurate" reporting were determined by examining comparable self-reports and performance measures. Logistic regression determined how much of the gender differential in self-reported function was explained by performance ability. RESULTS: More women than men reported disability and functional limitation, and women had poorer performance scores for every task. Compared to similar performance items, self-reports of function were accurate for the majority of men and women. However, among those who inaccurately reported function, more men than women underreported disability and more women than men overreported disability. Overall performance explains all of the gender difference in ADL disability and most of the difference in functional limitation. CONCLUSIONS: These results suggest that both men and women generally report their disability accurately, and women's higher prevalence of reported functional problems is probably a reflection of true disability for most disability measures.

Activities of Daily Living↗
PubMed1999

Gender differences in sympathetic nervous system regulation.

1. Females are protected against the development of hypertension. The purpose of the current review is to present the evidence for gender differences in the regulation of the sympatho-adrenal nervous system and to determine if these differences support the hypothesis that, in females, the regulation of the sympathetic nervous system (SNS) is altered such that sympatho-adrenal activation is attenuated or sympatho-adrenal inhibition is augmented. 2. The central control of sympatho-adrenal function is different in females and responses vary during the oestral and menstrual cycles. Pathways regulating the SNS appear to be less sensitive to excitatory stimuli and more sensitive to inhibitory stimuli in females compared with males. 3. Gender differences in arterial baroreflex sensitivity suggest that females may have a greater baroreflex sensitivity, such that alterations in blood pressure are more efficiently controlled than in males. Cardiopulmonary reflex inhibition of sympathetic nerve activity is greater in females, possibly resulting in a greater renal excretory function. 4. An attenuated sensitivity to adrenergic nerve stimulation, but not to noradrenaline (NA), suggests that gender differences in noradrenergic neurotransmission may protect females against sympathetic hyperactivity. Gender differences in the regulation of NA release via presynaptic alpha 2-adrenoceptors, the vasoconstrictor response to the cotransmitter neuropeptide Y and the clearance of catecholamines are consistent with this hypothesis. 5. Similarly, attenuated stress-induced increases in plasma catecholamines in women suggest that females are less sensitive and/or less responsive to adrenal medullary activation. This is supported by findings of gender differences in adrenal medullary catecholamine content, release and degradation. 6. We conclude that there is strong evidence that supports the hypothesis that, in females, the regulation of the SNS is altered such that sympatho-adrenal activation is attenuated or sympatho-adrenal inhibition is augmented.

Adrenal Medulla↗
PubMed2003

Decreasing gender differences in "avoidable" mortality in Sweden.

AIMS: "Avoidable" mortality, that is mortality from conditions amenable to healthcare intervention, is commonly studied as an indicator of the outcome of healthcare. The objective of this study was to analyse gender equity in avoidable mortality trends in Sweden from 1971 to 1996. METHODS: The underlying cause of death was analysed for all deaths in the Swedish population in the age group 0-69 years during the period 1971-96. On the basis of those used in international studies, 18 indicators of avoidable mortality were identified. The conditions were divided into two groups: those mainly indicating an outcome of medical care and those mainly reflecting the effect of health policy. Age-standardized death rates were calculated for each indicator of avoidable mortality and for total mortality broken down by sex. Gender differences in death rates were studied. The annual trends in death rates were analysed using regression models. RESULTS: For total mortality the death rates were 80% higher for males than for females. The largest gender differences were found among those conditions mainly reflecting the effects of health policy. For most medical care indicators the gender differences were fairly small. For several avoidable causes of death the gender differences decreased considerably and for some causes of death the differences were eliminated. CONCLUSIONS: The avoidable mortality method seems to be useful in continuous epidemiological surveillance of the equity in healthcare. The comparatively low gender differences for avoidable death indicators as well as the decrease in these differences indicate decreasing gender inequity in health.

Adolescent↗
PubMed2002

Gender difference in the glucagon response to glucopenic stress in mice.

A gender difference in the glucagon response to insulin-induced hypoglycemia was previously demonstrated in humans. Whether this reflects a gender difference in autonomic activation or in pancreatic alpha-cell regulation is not known. We investigated the glucagon, epinephrine, and norepinephrine responses to neuroglycopenic stress induced by 2-deoxy-D-glucose (2-DG) or insulin in female and male mice. 2-DG increased plasma glucagon levels by 559 +/- 68% in females versus 281 +/- 46% in males (P < 0.01). Plasma levels of epinephrine or norepinephrine after 2-DG administration did not differ between genders. During insulin-induced hypoglycemia, the glucagon response was similarly higher in females (P < 0.001), whereas the plasma catecholamine response was higher in males (P < 0.05). In vivo, the glucagon response to carbachol or clonidine was higher in females (P < 0.05). In isolated islets, the glucagon response to carbachol (100 microM; P = 0.003) but not to clonidine (1 microM) was larger in females. We conclude that in addition to a larger alpha-cell mass (previously described in female mice), an increased sensitivity of the glucagon-producing alpha-cell to cholinergic activation contributes to the larger glucagon response to glucopenic stress in female mice.

Adrenal Glands↗
PubMed2005

Gender differences in electrophysiologic effects of mental stress and autonomic tone inhibition: a study in health individuals.

INTRODUCTION: Gender differences exist in electrophysiologic properties and the occurrence of certain arrhythmias. Mental stress may trigger serious arrhythmias, including ventricular tachycardias and ventricular fibrillation. This study investigates gender differences in the electrophysiologic effects on different levels of the cardiac conduction system elicited by mental stress and autonomic tone inhibition. METHODS AND RESULTS: Twenty-three healthy volunteers (11 male and 12 female) participated in the study. Electrophysiologic and hemodynamic variables were measured at baseline, during mental stress produced by Stroop's color word conflict test (CWT), and after autonomic tone inhibition (ATI) with propranolol (0.15 mg/kg) and atropine (0.02 mg/kg). During CWT, men showed shorter QT and JT durations, whereas women had shorter refractoriness in the atrial tissue and AV node. After ATI, no gender differences in sinus nodal properties were noted, whereas AV nodal refractoriness and conduction time became shorter in women, and QT and JT duration and the refractory period of the right ventricle were shorter in men. CONCLUSION: In women, mental stress produces a pronounced effect on the AV node and on the sinus node. Men react with a more pronounced effect on ventricular electrophysiologic properties. Certain gender differences in cardiac electrophysiologic properties seem to be intrinsic. After ATI, women have a higher heart rate and shorter AV nodal refractoriness but longer QT and JT intervals and longer effective refractory periods in the right ventricle. These differences may partly explain why certain arrhythmias occur more often in women than in men.

Adrenergic beta-Antagonists↗
PubMed2005

Gender differences in Class III malocclusion.

This study evaluated gender differences in the cephalometric records of a large-scale cross-sectional sample of Caucasian subjects with Class III malocclusion at different developmental ages. The purpose also was to provide average age-related and sex-related data for craniofacial measures in untreated Class III subjects that are used as reference in the diagnostic appraisal of the patient with Class III disharmony. The sample examined consisted of 1094 pretreatment lateral cephalometric records (557 female subjects and 537 male subjects) of Caucasian Class III individuals. The age range for female subjects was between three years six months and 57 years seven months. The male subject group ranged from three years three months to 48 years five months. Twelve age groups were identified. Skeletal maturity at different age periods also was determined using the stage of cervical vertebral maturation. Gender differences for all cephalometric variables were analyzed using parametric statistics. The findings of the study indicated that Class III malocclusion is associated with a significant degree of sexual dimorphism in craniofacial parameters, especially from the age of 13 onward. Male subjects with Class III malocclusion present with significantly larger linear dimensions of the maxilla, mandible, and anterior facial heights when compared with female subjects during the circumpubertal and postpubertal periods.

Adolescent↗
PubMed2005

Gender differences in cognitive vulnerability to depression and behavior problems in adolescents.

This study assessed gender differences in cognitive variables as an explanation for gender differences in depression and behavior problems; 856 adolescents (491 females and 365 males), aged 14-17, completed the Irrational Beliefs Scale for Adolescents, the Social Problem Solving Inventory-Revised Short Form, the adolescent version of the Burnett Self-Talk Inventory, and the Youth Self Report. Female adolescents' lower levels of positive thinking and higher scores on negative problem orientation, need for approval and success, and self-focused negative cognitions partially mediated gender differences in depressive symptoms. Males' higher scores on justification of violence beliefs and the impulsivity/carelessness style of problem solving partially accounted for differences in delinquent behavior. The influence of need for approval and success on depressive symptoms was higher among adolescents at ages 14-15 than among older adolescents. Justification of violence did not influence delinquent behavior among girls at age 14-15.

Adolescent↗
PubMed1996

Gender differences in the expression of depressive symptoms among chronic pain patients.

OBJECTIVE: To investigate the extent to which gender differences in the expression of depressive symptomatology exist among chronic pain patients. SETTING: A multidisciplinary pain center affiliated with a state medical school in the southern United States. PATIENTS: A total general sample of 245 patients with heterogeneous chronic pain complaints randomly selected from a database of approximately 1,000 pretreatment evaluation patient files. A depressed subsample of 113 patients based on scores > or = 15 on the Beck Depression Inventory (BDI). MEASURE: The 21-item BDI. RESULTS AND CONCLUSIONS: Gender differences in total BDI scores were not revealed for the total general sample or depressed subsample, but gender differences in the expression of depressive symptoms (i.e., item level responses) were found via separate discriminant function analyses on the total general sample and depressed subsample. Consistent with previous studies performed on diverse samples, females' higher endorsement of body image distortion was noted in both of our samples. Females also endorsed significantly higher levels of fatigue in our total sample. Items that were not significant in our total sample include females' higher levels of loss of appetite and crying. In the depressed subsample, items probing pessimism and failure were not statistically significantly different to males' endorsing higher levels of each. Sensitivity to these gender differences is suggested in clinical practice. The likely consequences that these differences in the experience and expression of distress have on coping activities (e.g., help-seeking responses) and the reactions of others (e.g., health-care providers) are highlighted.

Adult↗
PubMed2002

Gender difference in the Oatp1-mediated tubular reabsorption of estradiol 17beta-D-glucuronide in rats.

The gender difference in the urinary excretion of estradiol-17beta-glucuronide (E(2)-17betaG) was examined in rats. The urinary clearance of E(2)-17betaG was >250 times lower in male than in female rats. No such major gender difference was observed in its biliary excretion or metabolism in kidney homogenate. Both plasma protein binding and inulin clearance were comparable in male and female rats, suggesting that this gender difference cannot be explained by glomerular filtration. The urinary clearance with respect to the plasma unbound E(2)-17betaG in male rats was <1% of the glomerular filtration rate, indicating its potential reabsorption by the kidney, and this increased to a level comparable with that found in female rats when dibromosulfophthalein was coinfused. A marked increase in E(2)-17betaG urinary excretion was also observed in male rats that had undergone orchidectomy. Testosterone injections given to female rats reduced the urinary excretion to a level comparable with that of control male rats. The concomitant change in the expression of the gene product for organic anion-transporting polypeptide Oatp1, of which E(2)-17betaG is a typical substrate, was found in the kidney membrane fractions after these treatments. These results suggest that urinary E(2)-17betaG excretion is subject to hormonal regulation and that the large gender difference can be explained by regulation in Oatp1-mediated reabsorption.

Absorption↗
PubMed2005

Gender differences in the relation of insulin-like growth factor binding protein-1 to cardiovascular risk factors: a population-based study.

OBJECTIVE: A possible involvement of insulin-like growth factor-I (IGF-I) and its binding protein IGFBP-1 in the pathogenesis of cardiovascular disorder has been suggested. However, few publications have addressed the gender differences in cardiovascular risk factors in relation to the IGF/IGFBP system. The aim of the present study was to study gender differences in the relationship between fasting serum levels of IGFBP-1 and cardiovascular risk factors in a normal population of men and women. DESIGN: Cross-sectional study. Patients A normal population of 273 men and women aged 20-74 years. MEASUREMENTS: A medical examination was performed and blood drawn in the morning after subjects had been fasting overnight. Before the examination, they were asked to fill out a questionnaire concerning lifestyle and psychosocial factors. RESULTS: Fasting IGFBP-1 was lower in men than in women and was positively correlated to age in men but not in women. The men had in general a more disadvantageous cardiovascular risk profile than women, with several indicators of the metabolic syndrome: higher blood pressure and higher serum levels of total cholesterol, triglycerides, low density lipoprotein cholesterol (LDL-C), plasma-glucose and insulin, as well as lower IGFBP-1. Women had lower physical activity, lower consumption of alcohol, and lower values on indicators of psychosocial and mental health but had a healthier diet. Our findings indicate that low circulating levels of IGFBP-1 are associated with the well-known risk factors of cardiovascular disease; however, the association showed a different pattern for men and women. In men we found a negative association with body mass index (BMI), insulin resistance and diastolic blood pressure, and a positive association with SHBG, cortisol and testosterone. For women low IGFBP-1 appears in negative associations with BMI, waist-hip ratio (WHR), insulin resistance and testosterone, and in positive associations with SHBG and cortisol. Significant gender differences in the correlation with IGFBP-1 are seen for testosterone, cortisol, SHBG, WHR and oestradiol. For HDL-C and diastolic blood pressure the gender difference in correlation was at the limit of significance (P < 0.10). CONCLUSION: Low circulating levels of IGFBP-1 are associated with the well-known risk factors of cardiovascular disease; however, the association showed a different pattern for men and women. The most marked gender differences in the correlation with IGFBP-1 are seen for testosterone, cortisol, SHBG, WHR, oestradiol, HDL-C and diastolic blood pressure. Our study emphasizes the importance of separate analyses for men and women. The results presented are a step towards gaining a better understanding of the gender differences in cardiovascular disease and in the regulation of IGFBP-1, though further prospective studies are needed.

Adult↗
PubMed2001

Gender differences in cardiovascular response to dementia caregiving.

PURPOSE: This study examined gender differences in cardiovascular responses to laboratory-based stress, as well as in ambulatory hemodynamic (i.e., blood pressure and heart rate) functioning among caregivers of persons with dementia. DESIGN & METHODS: Participants were 25 men and 25 women caregivers, matched on age, type of care recipient's dementia, and relationship to the care recipient. After cardiovascular reactivity to a laboratory-based caregiving stressor was assessed, the ambulatory hemodynamic functioning levels of caregivers were measured in caregivers' natural environments. RESULTS: Female caregivers displayed greater systolic and diastolic blood pressure reactivity to a laboratory-based stress task (i.e., discussing caregiving difficulties) compared with male caregivers (p < or =.01). In contrast, no gender differences were found for ambulatory hemodynamic functioning when aggregated overall or when in the presence of the care recipient. IMPLICATIONS: Laboratory-based findings suggest that female caregivers experience greater blood pressure reactivity to caregiving-related stress than do male caregivers. However, these laboratory-based gender differences may not generalize to differences in hemodynamic functioning in caregivers' daily lives.

Aged↗
PubMed2005

Gender differences in lower extremity coupling variability during an unanticipated cutting maneuver.

The purpose of this study was to determine if gender differences exist in the variability of various lower extremity (LE) segment and joint couplings during an unanticipated cutting maneuver. 3-D kinematics were collected on 24 college soccer players (12 M, 12 F) while each performed the cutting maneuver. The following intralimb couplings were studied: thigh rotation (rot)/leg rot; thigh abduction-adduction/leg abd-add; hip abd-add/knee rot; hip rot/knee abd-add; knee flexion-extension/knee rot; knee flx-ext/hip rot. A vector-coding technique applied to angle-angle plots was used to quantify the coordination of each coupling. The average between-trial standard deviation of the coordination pattern during the initial 40 % of stance was used to indicate the coordination variability. One-tailed t-tests were used to determine differences between genders in coordination variability for each coupling. Women had decreased variability in four couplings: 32 % less thigh rot/leg rot variability; 40 % less thigh abd-add/leg abd-add variability; 46 % less knee flx-ext/knee rot variability; and 44 % less knee flx-ext/hip rot variability. These gender differences in LE coordination variability may be associated with the increased incidence of ACL injury in women. If women exhibit less flexible coordination patterns during competition, they may be less able to adapt to the environmental perturbations experienced during sports. These perturbations applied to a less flexible system may result in ligament injury.

Adaptation, Physiological↗
PubMed2000

Gender differences in cognitive abilities at 2 years in ELBW infants. Extremely low birth weight.

Gender differences in cognitive abilities exist for children born at term. For very preterm infants uncertainty exists regarding the presence and extent of such differences and their relationship to perinatal brain injury and neurological impairment. This study examined gender differences in cognitive abilities in a cohort of 336 extremely low birth weight (ELBW) infants at 2 years corrected age. Infants were classified as at low or high perinatal risk at birth according to four perinatal risk factors. A subgroup of 33 neurologically impaired infants was identified. Outcome at 2 years was measured by the overall General Quotient (GQ) on the Griffiths scale and its five subscale scores. Female ELBW children were superior to male ELBW children by 4.1 GQ points (95% CI 1.0, 7.1). If the impaired subgroup was excluded, the difference in GQ was 3.2 points (95% CI 0.4, 5.6), and this difference was predominantly due to female infants being superior in the hearing and speech subscale (6.0 points, 95% CI 2.6, 9.5). These differences were relatively independent of perinatal risk status. Gender differences in the Griffiths GQ for ELBW infants are similar to expected differences for term infants and are unlikely to cause substantial bias in interpreting outcome studies for ELBW infants, unless these involve tests of specific cognitive abilities such as language.

Auditory Perception↗
PubMed1999

Gender differences in pharmacokinetics and pharmacodynamics.

Several years ago regulatory authorities requested to include women in all phases of clinical drug development in order to thoroughly investigate potential gender differences in the pharmacokinetics and pharmacodynamics of newly developed therapeutic agents. Since then, numerous reports have been published that evaluate the potential existence and impact of gender differences on all aspects of clinical pharmacology. With regard to pharmacokinetics, differences in absorption rate and duration have been reported for several drugs, but generally lack to have major clinical relevance. Differences in oral bioavailability, however, seem to be more important and are usually caused by sex differences in the activity of major intestinal and hepatic metabolic enzymes. Distributional differences have also been identified for numerous compounds. Although the majority of these findings were merely weight effects as women generally have a lower body weight, some of the gender-specific distribution differences persisted after normalization for weight. Possible explanations are differences in body composition between men and women and/or physiological changes during the menstrual cycle as well as differences in plasma protein binding secondary to hormonal characteristics. Frequent and sometimes clinically relevant gender differences could be identified for drug elimination processes and were predominantly linked to the sex-specific expression of metabolic enzyme systems, e.g. CYP3A4 and CYP1A2. In contrast, gender-related differences in renal elimination are generally only of minor importance. With regard to pharmacodynamics, gender differences have been observed in baseline characteristics as well as in drug response, which might both, at least in part, be the consequence of modulation by sex hormones. Some of the most striking examples identified were in pain therapy and perception, glucose management and arrhythmia susceptibility. Since clinical endpoints of efficacy and toxicity are often difficult to monitor and are frequently substituted by surrogate markers that might increase variability and thus mask gender effects, sex-specific differences in pharmacodynamic characteristics can often remain uncovered and further intensive research in this area seems imperative. For the majority of investigated drugs in the past few years, however, no or only very minor gender differences could be detected in pharmacokinetics and/or pharmacodynamics. In addition, the clinical significance of those gender differences identified seem very limited and was only very rarely linked to treatment success or failure. Hence, it is undoubtedly necessary to include women in the clinical drug development process, but it seems questionable whether women of child-bearing capability should be exposed to potential risks in early phase I clinical trials.

Administration, Oral↗
PubMed2005

Gender differences in head-neck segment dynamic stabilization during head acceleration.

PURPOSE: Recent epidemiological research has revealed that gender differences exist in concussion incidence but no study has investigated why females may be at greater risk of concussion. Our purpose was to determine whether gender differences existed in head-neck segment kinematic and neuromuscular control variables responses to an external force application with and without neck muscle preactivation. METHODS: Forty (20 females and 20 males) physically active volunteers participated in the study. The independent variables were gender, force application (known vs unknown), and force direction (forced flexion vs forced extension). The dependent variables were kinematic and EMG variables, head-neck segment stiffness, and head-neck segment flexor and extensor isometric strength. Statistical analyses consisted of multiple multivariate and univariate analyses of variance, follow-up univariate analyses of variance, and t-tests (P < or = 0.05). RESULTS: Gender differences existed in head-neck segment dynamic stabilization during head angular acceleration. Females exhibited significantly greater head-neck segment peak angular acceleration (50%) and displacement (39%) than males despite initiating muscle activity significantly earlier (SCM only) and using a greater percentage of their maximum head-neck segment muscle activity (79% peak activity and 117% muscle activity area). The head-neck segment angular acceleration differences may be because females exhibited significantly less isometric strength (49%), neck girth (30%), and head mass (43%), resulting in lower levels of head-neck segment stiffness (29%). CONCLUSION: For our subject demographic, the results revealed gender differences in head-neck segment dynamic stabilization during head acceleration in response to an external force application. Females exhibited significantly greater head-neck segment peak angular acceleration and displacement than males despite initiating muscle activity earlier (SCM only) and using a greater percentage of their maximum head-neck segment muscle activity.

Acceleration↗
PubMed2006

Gender differences in respiratory symptoms-does occupation matter?

Little attention has been given to gender differences in respiratory health, particularly in occupational settings. The purpose of this paper was to evaluate gender differences in respiratory morbidity based on surveys of hospitality workers, radiographers, and respiratory therapists. Data were available from mail surveys of 850 hospitality industry workers (participation rate 73.9%; 52.6% female), 586 radiographers (participation rate 63.6%; 85% female), and 275 respiratory therapists (participation rate 64.1%; 58.6% female). Cross-tabulations by gender were evaluated by chi(2) analysis and logistic regression with adjustment for personal and work characteristics. Women consistently had greater respiratory morbidity for symptoms associated with shortness of breath, whereas men usually had a higher prevalence of phlegm. There were few differences in work exposures apart from perception of exposure to ETS among hospitality workers. Gender differences in symptoms were often reduced after adjustment for personal and work characteristics but for respiratory therapists there were even greater gender disparities for asthma attack and breathing trouble. Population health findings of elevated symptoms among women were only partially supported by these occupational respiratory health surveys. The influence of differential exposures and personal factors should be considered when interpreting gender differences in health outcomes.

Adult↗
PubMed1997

[Gender differences in lifestyles of the middle-aged and the elderly--a study in Satomi village, Ibaraki, Japan].

The purpose of this study was to examine the gender differences in the total lifestyles of the middle-aged and the elderly. A self-administered questionnaire was employed to assess the lifestyles of inhabitants aged 40 years and over. Only 400 middle-aged and elderly who lived in Satomi village, Ibaraki Prefecture were randomly sampled for this study. Though the questionnaires contained 99 items such as nutrition, exercise, cigarette use, alcohol use, rest; we used only 84 items in this study. Satomi village is a rural area with a population size of approximately 4,500 and an aging rate of 25.9%. Questionnaires were sent to the subjects by mail. The response proportion was 90%, and the valid response proportion was 85.3%. Subjects included 155 men and 186 women. The average age of all subjects was 61.5 +/- 12.0 years old: males; 60.8 +/- 11.5 years old, females; 62.1 +/- 12.4 years old. Gender differences were assessed for selected items with the chi 2 test. Women tended to have significantly better health habits on items such as nutrition, alcohol intake, and cigarette use (p < 0.05). Factor analysis with varimax rotation was used to separate the items. Three factors that had eigenvalues substantially > 1.0 were extracted and explained 49.7% of the total variance. Factor 1 reflects health promotional activities; Factor 2 denotes health preventive activities; Factor 3 reflects the avoidance of health risk. Though gender differences were not observed for Factor 1 (p = 0.8647), they were seen for Factor 2 (p = 0.0003) and Factor 3 (p = 0.0001) with the Wilcoxon rank sum test. Wilks'lambda test was utilized as likelihood ratio test mean vectors of Factor 1, Factor 2, and Factor 3 (p = 0.0001). The results of the Wilks'lambda test indicated significant gender differences. Our findings suggest significant gender differences in the total lifestyles, but not in the individual lifestyle habits.

Aged↗
PubMed2002

Gender difference in the urinary excretion of organic anions in rats.

This study was aimed at clarifying the gender differences in the urinary excretion of organic anions and the gene expression of organic anion transporters in rats. The renal clearance with regard to the plasma concentration (CL(urine,p)) of taurocholate, dibromosulfophthalein (DBSP), and zenarestat, all substrates and/or inhibitors of organic anion transporting polypeptide 1 (Oatp1), was much higher in female than in male rats. The following results imply that the transport system(s) for the reabsorption of zenarestat across the luminal side exhibits a gender difference: 1) the renal uptake clearance assessed by an in vivo integration plot analysis of zenarestat from the blood side does not show any clear gender differences; 2) the renal clearance with regard to the kidney concentration (CL(urine,k)) of zenarestat in female rats was approximately 30 times higher than in male rats; and 3) both CL(urine,p) and CL(urine,k) were increased in male rats by the coinfusion of DBSP, which is an inhibitor of organic anion transporters. Northern and Western blot analyses confirmed a previous finding that the gene expression of Oatp1, which is localized at the apical plasma membrane of the kidney, was much higher in the kidneys of male rats. Overall, a gender difference in urinary excretion is commonly observed for several organic anions, including Oatp1 substrates and inhibitors, and Oatp1 and/or transporters that have a similar substrate specificity to Oatp1 could be involved in such a phenomenon involving its substrates.

Animals↗