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PubMed2005

Novel gender-related regulation of CYP2C12 gene expression in rats.

The expression of CYP2C12 by GH occurs in female but not in male rat livers. Direct injection of the CYP2C12 promoter-luciferase gene into male rat livers showed that the CYP2C12 promoter was active in both male and female rats. Thus, to further examine one or more factors that regulate the gender-related expression of CYP2C12, male rats were treated with trichostatin A, a specific inhibitor of histone deacetylase capable of condensing the chromatin structure. Interestingly, the expression of CYP2C12 by GH was seen even in the livers of male rats, indicating that histone deacetylase contributes to the suppression of CYP2C12 expression in male rats. Deoxyribonuclease I hypersensitive assay using nuclei from the livers of male or female rats revealed that the chromatin structure of the CYP2C12 gene was gender specific: a hypersensitive site at a position -4.2 kb containing GH-responsive element that bound to signal transducer and activator of transcription 5 (STAT5), termed as HS (hypersensitive site) 1, was specific for female rat livers, whereas a hypersensitive site at a position -3 kb, designated as HSm (male-specific hypersensitive site), was characteristic of male rat livers. A -3425/-3275 region within HSm functioned as a negative regulatory region, when the region was inserted in front of simian virus 40 promoter. Gel shift assay demonstrated that both CCAAT/enhancer-binding protein alpha and beta bound to the -3425/-3275 region. Based on these results, we conclude that the gender-related expression of the CYP2C12 gene results from the inaccessibility of to STAT5 to the GH-responsive element by chromatin condensation seen in male rat livers, and from the presence of the male-specific HSm that acts as a silencer.

5' Flanking Region↗
PubMed2003

Gender-related differences in concanavalin A-induced liver injury and cytokine production in mice.

BACKGROUND/AIM: Concanavalin A (Con A) activates T cells and causes T cell-mediated liver injury in mice. Since autoimmune diseases predominantly occur in women, female is considered to have enhanced immune responses and T cell functions. We investigated the presence of gender-related differences on Con A-induced liver injury and cytokine production in mice. METHODS: Male and female BALB/c mice were given Con A (15mg/kg) intravenously at 7 weeks of age. Plasma alanine aminotransferase (ALT), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), interleukin (IL)-4 and IL-10 levels were determined 0, 2, 4, 6, 8 and 24h after Con A administration. To investigate the effects of sex hormones on liver injury and cytokine production, female and male mice were castrated at 3 weeks of age and were administered Con A 4 weeks after the operation. RESULTS: Plasma ALT level of females was significantly higher at 8 and 24h after Con A administration than those of males. Plasma levels of TNF-alpha and IFN-gamma at 2, 4, 6 and 8h, IL-4 at 2h, but not IL-10, after Con A administration were significantly elevated in females than those of males. Furthermore, the elevated plasma ALT, TNF-alpha and IFN-gamma levels decreased significantly by an ovariectomy. In contrast, those markers were exacerbated by an orchiectomy compared with sham operation. CONCLUSION: These findings indicate that Con A induces more severe liver injury in female mice than in male mice, and suggest that the effect of sex hormones on cytokine production may play a role in gender-related difference on Con A-induced liver injury.

Journal Article↗
PubMed1997

Gender-related differences in androgen regulation of thromboxane A2 receptors in rat aortic smooth-muscle cells.

Thromboxane A2 (TXA2) has been implicated as an important mediator of cardiovascular diseases. Aortas obtained from male rats are more sensitive to TXA2 mimetics compared with those obtained from females. A similar phenomenon has been reported in canine coronary arteries. To determine whether there is a gender-related difference in the regulation of TXA2 receptors by androgenic steroids, we determined the effect of testosterone and dihydrotestosterone (DHT) on TXA2 receptor density in cultured rat aortic smooth-muscle (RASM) cells and guinea pig coronary artery smooth-muscle (CASM) cells. TXA2 receptor density (B(max)) and dissociation constant (Kd) were determined by radioligand binding studies with (125)I-BOP, a TXA2 receptor agonist. Testosterone significantly (p < 0.05) increased TXA2 receptor density in cultured RASM cells and guinea pig CASM cells. DHT significantly (p < 0.005) increased the B(max) in male RASM cells (62 +/- 2 vs. 40 +/- 3 fmol/mg protein; n = 7; p < 0.005). DHT increased the B(max) values in both male and female RASM cells, but the increase was significantly (p < 0.05) less in female than in male RASM cells (57 +/- 10% increase for male and 31 +/- 5% for female). Androgen-receptor protein was detected in RASM cells by Western blot and was less in the female RASM cells than in the male. The results indicate that RASM cells possess an androgen receptor and that gender-related differences exist in the regulation of expression of TXA2 receptors by androgens.

Androgens↗
PubMed2005

Gender related effects of heroin abuse on the simple reaction time task.

Accumulated studies have demonstrated that there are serious negative consequences of drug abuse, especially the impairment of central nervous system (CNS) function. The simple reaction time (SRT) is the simplest model of measuring the function of the CNS. The purpose of the present study is to examine whether the SRT is affected by heroin abuse and whether such drug effect, if exists, is gender related. We found significant slowing of the SRT in both male and female heroin dependent patients at 1-3 months from withdrawal. However, the SRT slowing remitted after 3 months of abstinence in heroin dependent males but not in females. Our results suggested that the SRT is slowed by heroin abuse and such slowing is gender related.

Adult↗
PubMed1996

Rat strain- and gender-related differences in neurobehavioral screening: acute trimethyltin neurotoxicity.

Trimethyltin (TMT) produces unique pathological and behavioral changes after a single dose. In this study, TMT was used to examine the ability of a neurobehavioral screening battery (functional observational battery and motor activity) to characterize these behavioral changes in rats. The behavioral profile of TMT was obtained using these tests in male Long-Evans (LE) and Fischer 344 (F344) rats, to assess the influence of rat strain, and in LE males and females to evaluate gender-related differences. All rats were tested before dosing and again at 1, 7, 21, and 42 d after a single dose of either 0, 4, 6, or 8 mg/kg TMT-hydroxide (intravenously). In general, the characteristic syndrome of tremor, increased reactivity, and hyperactivity was observed; however, the magnitude and time course of these effects were much greater in F344 rats. Significant strain- but not gender-related differences were obtained when comparing TMT effects on different domains of neurological function. Comparisons of predosing data between male LE and F344 rats, as well as between male and female LE rats, revealed significant differences in baseline values for about half of the measures of the test battery. These preexisting differences, however, could not account for the observed dissimilarities in treatment effects. Quantitative and qualitative differences were evident to a greater extent when comparing LEs and F344s than between males and females. Therefore, conclusions based on these types of neurobehavioral screening data would be influenced considerably more by the differences between rat strains.

Analysis of Variance↗
PubMed1994

Gender-related differences in the baroreceptor reflex control of heart rate in normotensive humans.

The present study investigates the baroreceptor reflex control of heart rate (HR) of normotensive male and female human volunteers under two conditions: bolus- and infusion-evoked elevations of blood pressure by intravenous administration of phenylephrine. Average age and blood pressure were similar in both sexes, but females had a significantly lower heart period (HP; higher HR). A major difference existed between the two sexes when the blood pressure was elevated by the bolus method. Females had a significantly (50%) smaller baroreflex sensitivity (regression coefficient), which inferred a gender-related difference in baroreceptor reflex control of HR. However, because a positive correlation existed between basal HP and baroreflex sensitivity, it was important to investigate whether this difference was related to the significantly lower basal HP in females. This possibility was ruled out because a similar difference still existed when the data were collected from another group of females who had basal HP values similar to those of males. This gender-related difference in baroreceptor reflex control of HR seems to depend on the pattern by which the pressor stimulus is evoked. The baroreceptor HP response to a slowly developing pressor response that was maintained at a steady-state level was very similar in both sexes. Because the HP response to abrupt (bolus-evoked) pressor stimuli mainly reflects the activity of the vagal component, our findings suggest that the cardiac vagal component seems to play a substantially smaller role in the baroreflex-mediated bradycardia in females.

Adult↗
PubMed1993

Dynamic gender-related differences in dichotic listening performance.

This experiment investigated dynamic gender-related differences in perceptual asymmetry (PA) in a dichotic task. Twenty right-handed males and 20 right-handed females performed a 200 trial directed attention dichotic listening task using consonant-vowel-consonant nonsense syllables. Men showed a greater right-ear advantage (REA) at the beginning of the test than did women. Over the course of the test the REA in men declined significantly (P < 0.001) whilst in females the REA showed a significant increase (P < 0.001). Thus by the end of the test the REA was greater in females than males. However, the reduced REA in males was entirely due to improved left-ear (LE) performance and the increased REA in females was due to improved right-ear (RE) performance. The change in PA in women is consistent with a dynamic improvement in left hemisphere (LH) syllable processing and in men a dynamic improvement in the transmission of information through the right hemisphere (RH) to the language processing areas in the LH.

Adult↗
PubMed2006

Gender-related differences in lateralization of hippocampal activation and cognitive strategy.

Gender-related differences in brain activation patterns and their lateralization associated with cognitive functions have been reported in the field of language, emotion, and working memory. Differences have been hypothesized to be due to different cognitive strategies. The aim of the present study was to test whether lateralization of brain activation in the hippocampi during memory processing differs between the sexes. We acquired functional magnetic resonance imaging data from healthy female and male study participants performing a spatial memory task and quantitatively assessed the lateralization of hippocampal activation in each participant. Hippocampal activation was significantly more left lateralized in women, and more right lateralized in men. Correspondingly, women rated their strategy as being more verbal than men did.

Adult↗
PubMed2003

Androgen contributes to gender-related cardiac hypertrophy and fibrosis in mice lacking the gene encoding guanylyl cyclase-A.

Myocardial hypertrophy and extended cardiac fibrosis are independent risk factors for congestive heart failure and sudden cardiac death. Before age 50, men are at greater risk for cardiovascular disease than age-matched women. In the current studies, we found that cardiac hypertrophy and fibrosis were significantly more pronounced in males compared with females of guanylyl cyclase-A knockout (GC-A KO) mice at 16 wk of age. These gender-related differences were not seen in wild-type mice. In the further studies, either castration (at 10 wk of age) or flutamide, an androgen receptor antagonist, markedly attenuated cardiac hypertrophy and fibrosis in male GC-A KO mice without blood pressure change. In contrast, ovariectomy (at 10 wk of age) had little effect. Also, chronic testosterone infusion increased cardiac mass and fibrosis in ovariectomized GC-A mice. None of the treatments affected cardiac mass or the extent of fibrosis in wild-type mice. Overexpression of mRNAs encoding atrial natriuretic peptide, brain natriuretic peptide, collagens I and III, TGF-beta1, TGF-beta3, angiotensinogen, and angiotensin converting enzyme in the ventricles of male GC-A KO mice was substantially decreased by castration. The gender differences were virtually abolished by targeted deletion of the angiotensin II type 1A receptor gene (AT1A). Neither castration nor testosterone administration induced any change in the cardiac phenotypes of double-KO mice for GC-A and AT1A. Thus, we suggest that androgens contribute to gender-related differences in cardiac hypertrophy and fibrosis by a mechanism involving AT1A receptors and GC-A.

Androgen Receptor Antagonists↗
PubMed2006

Age and gender related changes in biomechanical properties of healthy human costal cartilage.

BACKGROUND AND AIMS: For repairing the ear malformation, it is recommended in China to use the over than 10-years-old rib cartilage. However, according to our clinical experience, a better post-operation effect can be found using about the 7-years-old cartilage for the operation. To shape a harvested costal cartilage and to perform it on the transplant site depend on the mechanical properties of the costal cartilage. Hence, the aim of this study is to investigate the age and gender-related biomechanical properties of the human costal cartilage. METHODS: Human costal cartilages were harvested from 25 female and 45 male donors of 5-25 years old after auricular reconstructive surgery. The specimens were divided into six groups: children (5-10 years), adolescent (11-17 years) and adult (18-25 years), respectively, in males and females. Tensile strength, stress-strain relationship, stress relaxation and creep were tested by using a material testing machine. FINDINGS: The biomechanical properties of costal cartilage are donor age and gender related. The children group has the highest tensile strengths (P<0.01) in both male and female groups. The male group relaxed and crept more than that of the female group in all three age groups (P<0.01). INTERPRETATION: These findings provide a further support for the potential age acting on the human costal cartilage. The adolescent has the lowest strength, this could be a reason that compared to using the children costal cartilage, the bigger distortion happened after using the adolescent costal cartilage in the auricular reconstruction operation.

Adolescent↗
PubMed2000

Gender-related traits in gay men, lesbian women, and heterosexual men and women: the virtual identify of homosexual-heterosexual diagnosticity and gender diagnosticity.

Three studies investigated the relationship between gender-related traits and sexual orientation. Study 1 showed that gay men and lesbians in an unselected sample of 721 college students differed from same-sex heterosexuals most strongly on gender diagnosticity (GD) measures, which assess male- versus female-typicality of interests (effect sizes of 2.70 for men and .96 for women) and least strongly on measures of instrumentality (I) and expressiveness (E). In Study 2, GD measures showed large differences between 95 gay and 136 heterosexual men (effect sizes of 1.61 and 1.83) and between 46 lesbian and 225 heterosexual women (effect sizes of .98 and 1.28), whereas I and E showed much smaller differences. In Study 3, GD showed large differences between 90 gay and 81 heterosexual men (effect sizes of 1.76 and 1.97) and between 82 lesbians and 108 heterosexual women (effect sizes 1.67 and 1.70). whereas I and E showed much smaller differences. Using data from Studies 2 and 3, "gay-heterosexual diagnosticity" measures were computed for men and "lesbian-heterosexual diagnosticity" measures for women, based on occupational and hobby preferences. These measures correlated very strongly with GD measures.

Adult↗
PubMed2000

Gender-related sleep differences in neonates in thermoneutral and cool environments.

Although thermoregulation and sleep exhibit gender differences in adults, the question is still debated in neonates. The aim of this study was to examine the relationship between gender-related sleep differences and cool defence mechanisms in neonates. Sleep and thermoregulation were recorded in healthy preterm neonates (21 boys and 17 girls, 37 +/- 2 weeks post-conceptional age) exposed to thermoneutral and cool conditions. Sleep was analysed for continuity and structure. Although the cool exposure did not strongly impair body homeothermia, sleep was altered but without any significant gender difference. However, when data recorded under each of the thermal conditions were pooled, some gender differences emerged: boys slept less, with more wakefulness after sleep onset, more active sleep and less quiet sleep than girls. In contrast to sleep architecture, most of the sleep continuity parameters exhibited greater variability in boys than in girls. This variability may bias the statistical analyses and probably explains the varying conclusions reported in the literature regarding gender-specific sleep-related differences.

Body Temperature Regulation↗
PubMed1994

Placebo effect on the circadian rhythm period tau of temperature and hand-grip strength rhythms: interindividual and gender-related difference.

Two different medications, one assumed to be a tranquilizer and the other an antifatigue agent, were tested. Both were found to be ineffective and thus were viewed as placebos and named P1 and P2. The effect of P1 and P2 on the circadian rhythms of a set of variables (e.g., sleep/wake, oral temperature and grip strength of both hands) were monitored by five to 10 measurements per day over three consecutive 8- to 10-day spans. The first documented span was a control (no medication), and the second and third spans (in randomized order) were under P1 and P2. Healthy subjects volunteered for the studies: nine men and seven women (median age 28 years) in study 1 and 12 men and 12 women (median age 36 years) in study 2. They were synchronized with diurnal activity from 07:00 h (+/- 30 min) to 00:00 h (+/- 1 h) and nocturnal rest. De Prins' method was used to obtain the prominent period tau in each (control, P1, and P2) individual time series. The chi 2 test was used to test group and subgroup differences. All 40 subjects exhibited a significant sleep/wake rhythm with a tau = 24 h in control, P1, and P2 series. During the control span a gender-related statistically significant difference was observed: fewer men than women exhibited a temperature rhythm desynchronized from 24 h. In addition, more women than men had a tau < 24 h during control. The gender-related difference was obliterated by placebos. Similarly desynchronized circadian rhythms of left and right hand-grip strength were observed in both men and women during the control span, which were all obliterated by placebo but only in men. Results are discussed with regard to a genetic model of human dyschronism as proposed by the authors.

Adult↗
PubMed1998

Effect of modulators of protein tyrosine kinase activity on gender-related differences in vascular reactivity at reduced temperature.

We used the isolated-muscle-bath technique to examine the effect of protein tyrosine kinase (PTK) and protein tyrosine phosphatase (PTP) inhibitors on the response of rings of tail artery from male and female rats to cooling and reduced temperature in the absence and presence of two PTK-dependent (clonidine and serotonin) and one PTK-independent (phenylephrine, PE) agonists. At 37 degrees C, reactivity to clonidine, serotonin, and PE was the same in tail artery from female and male rats. At 25 degrees C, reactivity to clonidine and serotonin, but not PE, was greater in tail artery from female rats compared with those from male rats. Sodium orthovanadate (SOV) eliminated the gender-related difference in the contractile effect of clonidine and serotonin at 25 degrees C. The sensitivity to relaxation by genistein was considerably greater for clonidine and serotonin at both temperatures as compared with PE. At 25 degrees C the sensitivity to genistein was greater for the clonidine and serotonin-contracted rings from female rats. In the presence of SOV, temperature reduction led to contraction of rat-tail artery. This effect was greater in rings from female rats. Our results strongly implicate differences in the activity of the PTK transduction pathway as the cause of the observed gender-related differences in agonist-mediated contraction at 25 degrees C and in cold-induced vasoconstriction.

Animals↗
PubMed2003

Gender-related differences in pharmacological relapse prevention with flupenthixol decanoate in detoxified alcoholics.

A study recently finished by our research group elucidated the effectiveness of flupenthixol decanoate (FLX) in maintaining abstinence in detoxified alcoholics. Flupenthixol decanoate is an established antipsychotic drug, which is well known for its mild antidepressant and anxiolytic activity as well as for its minimal sedation at low doses. It blocks dopamine binding at a number of receptor subtypes, primarily at D-1, D-2, D-3 and with less affinity at D4-receptors. It also affects serotonin binding at 5-HT2A and 5-HT2C receptors. In a double-blind placebo-controlled multicenter trial, 77 women and 204 men suffering from moderate or severe DSM-II-R alcohol dependence were randomly assigned to either 10 mg FLX or placebo both injected every second week over a period of 24 weeks (treatment phase) succeeded by a medication-free 24-weeks follow-up period. In the overall analysis the number of patients relapsed after 24 weeks of treatment (=main criterion of efficacy) was significantly higher in the FLX treated group (85.2%) than under placebo (65.5%). However, when differentiating this result according to sex the analysis revealed a gender-related discrepancy: while male patients had an almost 4-fold higher risk to relapse under FLX than under placebo (OR=3.95) this risk was barely elevated for female patients (OR=1.51). A significantly negative outcome due to FLX treatment was restricted to male alcoholics solely. In conclusion, gender-related differences to pharmacological relapse prevention with FLX have probably contributed to a better treatment outcome in women than in men.

Adult↗
PubMed2003

Contactless magnetocardiographic study of ventricular repolarization in intact Wistar rats: evidence of gender-related differences.

INTRODUCTION: Magnetocardiographic (MCG) mapping is increasingly used for the non-invasive study of coronary artery disease (CAD), cardiomyopathy (CMP) and arrhythmias. MCG study of small animals with ischemia or CMP would provide useful experimental models for the interpretation of abnormal human patterns. The aim of this study was to assess the range of normality of MCG ventricular repolarization parameters, in intact adult rats. METHODS AND RESULTS: 10 adult Wistar rats (weight 250 - 350 grams) were investigated with a 36-channel MCG mapping instrumentation (sensitivity is 20 fT/ radical Hz, at 1 Hz), designed for clinical recordings in unshielded hospital laboratories. To assess ventricular repolarization, MCG Q-T(peak), Q-T(end), J-T(peak), J-T(end), T(peak)-T(end) intervals were measured. MCG imaging was obtained by automatic calculation of isofield contour maps, and with inverse source localization based on the Equivalent Current Dipole and Effective Magnetic Dipole models, in a semi-infinite space with homogeneous conductance. Magnetic field (MF) orientation, dynamics and stability during the J-T(end) segment were also calculated. After averaging 300 s of continuous MCG recording, the S/N ratio was good enough for reproducible reconstruction of both atrial and ventricular magnetic maps and for three-dimensional localization of the underlying cardiac generators. Clear gender-related differences in ventricular repolarization duration were found, evidenced by significantly longer Q-T(end), J-T(end) and T(peak)-T(end) intervals in females. The differences in MF orientation, and stability during the J-T(end) segment were not significant. For J-T(peak) MF dynamics, only the ratio between the strengths of the positive and negative poles was significantly lower in the female group ( p < 0.05). CONCLUSIONS: Contactless MCG recording is a novel approach, which simplifies non-invasive mapping in small animals. In normal rats, gender-related differences of ventricular repolarization parameters equivalent to those reported in previous ECG studies were demonstrated.

Animals↗
PubMed2001

Gender-related differences in the onset of panic disorder.

OBJECTIVE: To investigate gender-related differences in premorbid conditions and in the role of triggering events in the onset of panic disorder (PD). METHOD: One hundred and eighty-four out-patients with a principal diagnosis of PD (DSM-IV) were evaluated with a semi-structured interview to generate Axis I and Axis II diagnoses according to DSM-IV, to collect family history of psychiatric disorders and life events. The statistical analysis was performed comparing men and women. RESULTS: Men and women showed similar age at onset of PD. A family history of mood disorders characterized females. Men had higher rates of cyclothymia, body dysmorphic disorder and depersonalization disorder preceding PD, while women had higher rates of bulimia nervosa. Dependent and histrionic PDs were more common among women, while borderline and schizoid PDs were more common among men. Life events showed a significant role in precipitating PD onset in women. CONCLUSION: Premorbid clinical conditions of PD seem to differentiate between males and females in the role of precipitating events.

Adult↗
PubMed2002

Improving medical students' comfort with, and skill in handling, gender-related inquiries during the residency selection process.

OBJECTIVE: Previous work has identified that medical students experience instances of gender discrimination and sexual harassment during the residency selection process (i.e., "audition" elective rotations, residency interviews, and career counseling).(1,2) Examples of such instances include male students who report being counseled away from obstetrics-gynecology and a female student who reported being asked about her sexual orientation because of an expressed interest in breast disease. Students also report confusion about what constitutes an appropriate question or inappropriate gender-related comments. A common example is questioning about plans for child care during residency. We developed an education intervention focused on gender- and family-related issues that may arise during the residency selection process in an attempt to improve our students' ability to (1) recognize appropriate and inappropriate questions and situations and (2) handle such situations in a professional manner. DESCRIPTION: Our educational intervention is a voluntary, intense, active learning situation composed of four parts. First, data outlining the problem-including personal stories of students-are presented. Second, a faculty member with dual experience as a residency training director and dean for student affairs presents examples of appropriate and inappropriate questions (both types of questions can be uncomfortable if not contemplated in advance), potential ways to approach these questions, and a thoughtful approach for the student to take when integrating his or her experiences during the residency selection process with ultimate decisions about career and ranked programs. During the third part of the workshop, students draw two cases of 15 potential situations from a hat. They work in pairs, first to identify whether the case outlines an appropriate or inappropriate situation and second to develop and practice their responses. The session concludes with open discussion about the various scenarios and responses. DISCUSSION: This workshop has been well received by our medical students. In post-workshop surveys, students universally reported that the session was useful. Ninety percent of attendees felt better able to recognize appropriate and inappropriate questions and situations during the residency selection process. Seventy-seven percent of students reported that they felt better able to handle inappropriate situations during the residency selection process in a professional manner. Student comments reflected great satisfaction with the interactive nature of the exercise, interest in expanding the amount of time dedicated to the workshop, and a desire for clear rules about what can/cannot be said. Faculty offering the workshop reported satisfaction doing the workshop and noted that the greatest challenge in presenting the material is balancing the discussion about reasonable responses to inappropriate behaviors with the students' interest in performing well on all interviews in order to maximize their options. Interest in the program has resulted in the authors' being invited to share the workshop at an upcoming GME retreat for the institution's program directors. Based on these results we plan to continue the workshop in an expanded version. In addition, we plan to use this format of the workshop as a springboard for similar sessions for medical students interested in confronting issues of discrimination and harassment in the educational setting.

Female↗