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PubMed1978

[Blood and cardiac cholinesterase activity in rats of different sexes and ages during muscle loading and hypokinesia].

The activity of acetylcholinesterase (Ache) and butyrilcholinesterase (Bche) in the blood and the heart of 3 and 13-month old control male rats is considerably lower than in female rats. In old rats (25 months) no sex differences in the Ache and Bche were revealed in the heart. In 3 and 13-month old male and female rats, under conditions of muscular exercises, the Ache and Bche activity is lower, and in hypokinetic male rats--higher than that in respective control animals. In all the rats, irrespective of sex, age and motor conditions, the Ache and Bche activity tended to decrease, in direction from the sino-atrial node to the heart apex.

Acetylcholinesterase↗
PubMed1983

[Features of the effects of apomorphine on rats of different sexes preferring ethyl alcohol].

The influence of apomorphine (1 mg/kg/day subcutaneously) on the behavior and some pharmacokinetic parameters of both male and female rats preferring ethanol to water was studied experimentally. Upon withdrawal of ethanol, apomorphine decreased the time of transmission to water consumption in the rats of both sexes and prevented a decline in the endogenous ethanol levels, the latter effect being especially pronounced in the female rats. Investigations on the "Animex" actograph showed an intensified response to apomorphine in rats preferring ethanol, with female rats displaying a greater change in the response. Under conditions of a renewed access to ethanol, apomorphine increased the time of the restoration of the previous preference for ethanol to water (with a stronger effect seen in females) and lowered the rate of ethanol elimination from the blood (in the female rats exclusively). The effacement of the sex differences in ethanol addicted rats, and a greater damaging impact of ethanol on female rats are emphasized.

Alcoholism↗
PubMed1987

Glutathione content and GSH S-transferase activity in midgut gland of Procambarus clarkii. Sex differences, the effect of fasting, and their implications in cadmium toxicity.

1. Glutathione content and GSH S-transferase activity in the midgut gland of Procambarus clarkii (P. c.) of different sex and body weight are presented. 2. Procambarus clarkii females' GSH concentration in the midgut gland decreases to a higher extent upon fasting, compared with males. 3. Procambarus clarkii females, both in control and fasting conditions, have a slightly higher GSH S-transferase activity than males. 4. Cadmium present in water only affects GSH content and GSH S-transferase activity (after 96 hr) in midgut gland, with cadmium chloride concentrations higher than 100 micrograms/l.

Animals↗
PubMed2003

Sex difference in the proliferative response of mouse hepatocytes to treatment with the CAR ligand, TCPOBOP.

The nuclear receptor Constitutive Androstane Receptor (CAR) binds DNA as a heterodimer with the retinoic-X receptor and activates gene transcription. Previously, in vitro studies have shown that the testosterone metabolites, androstenol and androstenol, inhibit the constitutive transcriptional activity of CAR, suggesting that differences might exist in the response to CAR-mediated gene activation between different sexes. In this study, we have analyzed the response of female and male CD-1 mice to stimulation of hepatocyte proliferation caused by the CAR ligand TCPOBOP. Results showed that the labelling index of female hepatocytes at 24, 30 and 36 h after treatment was much higher than that found in males. The higher proliferative activity of female hepatocytes was associated with increased hepatic levels of cyclin D1, cyclin A, E2F and enhanced phosphorylation of pRb and p107. The increased mitogenic response of females was associated with higher mRNA levels of CYP2B10, a known target of CAR. Administration of androstenol to TCPOBOP-treated mice caused a reduction of labelling index, which was accompanied by a decrease of CYP2B10 and CAR mRNA levels. In conclusion, the results show that, in addition to microsomal detoxification, another biological response elicited by the CAR ligand TCPOBOP, namely, hepatocyte proliferation, occurs at higher levels in female than male mice, suggesting that CAR transcriptional activity in males is partially counteracted by physiological higher levels of testosterone metabolites such as androstenol and androstenol.

Androstanols↗
PubMed1997

Reversal of the sex difference in serum leptin levels upon cross-sex hormone administration in transsexuals.

Women have higher circulating leptin levels than men. This sex difference is not simply explained by differences in the amount of body fat and is possibly influenced by their different sex steroid milieus. This prompted us to study prospectively the effects of cross-sex steroid hormones on serum leptin levels in 17 male to female transsexuals and 15 female to male transsexuals. Male to female transsexuals were treated with 100 micrograms ethinyl estradiol and 100 mg cyproterone acetate (antiandrogen) daily, and female to male transsexuals received testosterone esters (250 mg/2 weeks, im). Before and after 4 and 12 months of cross-sex hormone treatment, serum leptin levels and measures of body fatness were assessed. Before treatment, female subjects had higher serum leptin levels than male subjects independently of the amount of body fat (P < 0.01). Cross-sex hormone administration induced a reversal of the sex difference in serum leptin levels. Estrogen treatment in combination with antiandrogens in male subjects increased median serum leptin levels from 1.9 ng/mL before treatment to 4.8 ng/mL after 4 months and 5.5 ng/mL after 12 months of treatment (P < 0.0001). Testosterone administration in female subjects decreased median serum leptin levels from 5.6 to 2.6 ng/mL after 4 months and to 2.5 ng/mL after 12 months (P < 0.0001). Analysis of covariance revealed that the changes in serum leptin levels were independent of changes in body fatness in both groups (P < 0.01). In conclusion, these results indicate that sex steroid hormones, in particular testosterone, play an important role in the regulation of serum leptin levels. The prevailing sex steroid milieu, not genetic sex, is a significant determinant of the sex difference in serum leptin levels.

Adipose Tissue↗
PubMed1980

Sex difference of mercuric chloride-induced renal tubular necrosis in rats--from the aspect of sex differences in renal mercury concentration and sulfhydryl levels--.

When doses of 0.3 to 2 mg/kg of mercuric chloride were intravenously administered to rats of the JCL-SD strain, acute renal tubular necrosis was produced in the straight portion of the proximal tubules with a pronounced sex difference, the male being more susceptible. Necrosis was inhibited by castration of male rats and promoted by testosterone pretreatment. When 0.15 mg of mercury per rat was injected to adult rats, females showed higher levels of mercury in the whole kidney, outer cortex and inner cortex. Castration of male rats caused elevated renal levels of mercury and pretreatment with testosterone of females lowered the levels. Renal levels of sulfhydryl groups were higher than male rats and castrated male rats showed elevated renal levels. The sex difference in the levels of sulfhydryl groups seems to be one factor which causes different susceptibility to mercury between males and females.

Acute Kidney Injury↗
PubMed2002

Is there a "bladder sex"? The relation of different sex hormones and sex hormone receptors in bladder in childhood.

The aim of this study was to review the classical concept of bladder physiology in regard to sex hormone effects and to focus on a new concept. Sex hormones affect bladder functions and the classical concept tries to explain these effects via alpha and beta adrenoreceptors. The effects of hormones had been investigated in this understanding. To obtain a biological response to steroids in target tissues, specific proteins--so-called receptors--are warranted. After the demonstration of the sex hormone receptors in bladder first in adults and in children urge questioning the effects of hormones in this regard. The hypothesis is based on the fact that, if a special receptor is present, the direct (via sex hormone receptors) effect is more likely to occur as an indirect effect (via alpha and beta adrenoreceptors). There is evidence that there is a sex difference and the sex receptors and hormones play an important role in some bladder disorders. Therefore we stress the importance of investigating especially the pediatric patients with bladder problems in regard to sex hormone receptors and hormonal status.

Child↗
PubMed1990

Effect of streptozotocin-induced diabetes on sex differences in biliary lipid secretion in the rat.

Diabetes mellitus is often associated with lipid abnormalities that may differ with sex. In this work we studied biliary lipid secretion in male and female anaesthetized Wistar rats (250 g). Diabetes was induced by a single intraperitoneal injection of streptozotocin (6 mg/100 body weight) 6 days before carrying out the studies on bile secretion. Our results confirm the existence of sex differences in bile formation and composition, most of them probably due to a higher (+27%) bile acid output in the female animals. Diabetes induced profound alterations in these sex differences. (a) Bile flow was reduced in both sexes, but more markedly so in female diabetic rats; thus the difference observed in healthy animals was reduced (from 2.22 to 1.58 and from 1.84 to 1.40 microliters/min per g liver in female and male rats, respectively). (b) Bile acid and phosphatidylcholine outputs were increased to a similar extent (bile acid output: from 46.7 to 55.8 nmol/min per g liver, in females and from 36.8 to 50.7 nmol/min per g liver, in males; phosphatidylcholine output: from 3.3 to 13.1 nmol/min per g liver, in females and from 4.5 to 12.5 nmol/min per g liver, in males), and hence the sex differences were abolished. (c) Cholesterol output was increased in both sexes, but this enhancement was significantly higher in female rats (from 0.75 to 1.31 and from 0.65 to 0.89 nmol/min per g liver, in females and males, respectively). (d) The fractional pool of phospholipid species secreted into bile was different in female compared with male rats. The percentage of phosphatidylcholine was higher in female than in male healthy rats. Streptozotocin treatment reversed this proportion, which suggests that changes in the phospholipid composition of the canalicular plasma membrane may play a role in the observed alterations in biliary lipid secretion during diabetes mellitus. Most of the above-described streptozotocin-induced changes were prevented by insulin replacement from the 3rd to the 6th days after streptozotocin injection. In summary, the present study describes alterations in sex differences in biliary lipid secretion of streptozotocin-induced diabetes. These changes are dependent on the insulin deficiency state rather than on a direct hepatotoxicity of the diabetogenic drug.

Animals↗
PubMed2006

Sex differences and the role of sex steroids in renal injury.

PURPOSE: There is growing evidence that significant sex differences exist in the response of the kidney to injury. In this review we explored the cumulative clinical knowledge and experimental evidence of this phenomenon. MATERIALS AND METHODS: The current clinical evidence of increased male susceptibility to acute and chronic renal injury, and experimental data elucidating potential mechanisms of this phenomenon were reviewed. RESULTS: Renal damage induced by nephron reduction, patient age and renal ischemia is tolerated differently by the sexes. Sex differences in disease susceptibility have historically been attributed to the protective effects of estrogen but recent evidence suggests that male hormones also have an important role in these differences. Vascular mediators, such as endothelin, nitric oxide and angiotensin II, appear to be influenced by sex and sex steroids. Additionally, inflammatory mediators, such as transforming growth factor-beta1, tumor necrosis factor-alpha and p38 mitogen activating protein kinase, similarly show differential expression and activity based on sex and the presence of sex steroids. These mediators have a significant impact on the kidney response to inflammation and injury. CONCLUSIONS: Greater understanding of the specific role of sex steroids in renal injury may provide new therapeutic strategies to protect against inflammatory injury and renal damage in the future.

Animals↗
PubMed1998

Double duty for sex differences in the brain.

Sex differences have been found in the anatomy of brains of a wide variety of vertebrates including humans. Common lore tells us that sex differences in the brain cause sex differences in behavior. This review entertains the possibility that sex differences in the brain may also do the exact opposite. Specifically, sex differences may allow males and females to display remarkably similar behaviors, despite major differences in their physiological and hormonal conditions. First, the difficulties in interpreting the relationship between structure and function will be illustrated by discussing the role of the sexually dimorphic medial preoptic area (MPOA) in male sexual behavior and parental behavior. Second, the sexually dimorphic vasopressin innervation of the brain will be presented as a system that appears to promote as well as prevent sex differences in behavior. Finally, basic and clinical aspects of sex differences in human brains will be discussed.

Animals↗
PubMed1997

Sex differences in pain.

Are there sex differences in pain? For experimentally delivered somatic stimuli, females have lower thresholds, greater ability to discriminate, higher pain ratings, and less tolerance of noxious stimuli than males. These differences, however, are small, exist only for certain forms of stimulation and are affected by many situational variables such as presence of disease, experimental setting, and even nutritive status. For endogenous pains, women report more multiple pains in more body regions than men. With no obvious underlying rationale, some painful diseases are more prevalent among females, others among males and, for many diseases, symptoms differ between females and males. Sex differences in attitudes exist that affect not only reporting, coping, and responses to treatment, but also measurement and treatment. So many variables are operative, however, that the most striking feature of sex differences in reported pain experience is the apparent overall lack of them. On the other hand, deduction from known biological sex differences suggests that these are powerful sex differences in the operation of pain mechanisms. First, the vaginal canal provides an additional route in women for internal trauma and invasion by pathological agents that puts them at greater risk for developing hyperalgesia in multiple body regions. Second, sex differences in temporal patterns are likely to give rise to sex differences in how pain is "learned" and stimuli are interpreted, a situation that could lead to a greater variability and wider range of pains without obvious peripheral pathology among females. Third, sex differences in the actions of sex hormones suggest pain-relevant differences in the operation of many neuroactive agents, opiate and nonopiate systems, nerve growth factor, and the sympathetic system. Thus, while inductive analysis of existing data demonstrate more similarities than differences in pain experience between females and males, deductive analysis suggests important operational sex differences in its production.

Adult↗
PubMedDate not supplied

Interdisciplinary research is key to understanding sex differences: report from the Society for Women's Health Research Meeting on understanding the biology of sex differences.

Progress in sex-based biology, the study of biological and behavioral differences between males and females, and the impact of those differences on health and disease will require collaboration across research disciplines and medical specialties and among all research approaches, from molecular biology to epidemiology. The importance of sex-based biology to healthcare necessitates a bench-to-bedside approach that is built on integration of research findings from studies at the cellular level, in animals, and in human subjects. Barriers to interdisciplinary collaborations are being addressed in a variety of ways by public and private funders. The J.D. and C.T. MacArthur Foundation supports interdisciplinary research networks that address broad questions in health and behavior. The National Institute of Mental Health supports cross-disciplinary research networks investigating the hypothalamic-pituitary-adrenal network. The National Institute of Child Health and Human Development offers grants for Building Interdisciplinary Research Careers in Women's Health. The National Science Foundation Directorate for Biological Sciences sponsors Research Coordination Networks in Biological Sciences. Among the challenges faced by interdisciplinary research programs are appropriate peer review, career advancement for young investigators with interdisciplinary training, and acceptance of interdisciplinary research reports by high-quality scientific publications.

Female↗
PubMed1991

Dopamine content and metabolism in mesencephalic and diencephalic cell cultures: sex differences and effects of sex steroids.

Sexual differentiation of dopaminergic neurons was studied in gender-specific cultures. Dissociated cell cultures were prepared from di- or mesencephalon of gestational day 14 rat embryos and raised in the absence or presence of 17 beta-estradiol or testosterone for up to 13 days in vitro (DIV). Developmental profiles of levels of dopamine (DA) and metabolites as well as capacity for vesicular storage of the transmitter were determined by HPLC. Tyrosine hydroxylase-immunoreactive (TH-IR) neurons were counted. Higher levels of DA were measured in female than in male cultures of both brain regions. In mesencephalic cultures, the differences in DA levels were fully accounted for by sex differences in numbers of TH-IR cells, whereas no sex differences in cell numbers were found in diencephalic cultures. Dihydroxyphenylacetic acid (DOPAC) levels and vesicular storage capacity matured faster in mesencephalic than in diencephalic cultures, but no sex differences were observed. Homovanillic acid (HVA) could not be detected except in 13-DIV mesencephalic cultures. Hormonal treatment did not erase sexual differentiation of dopaminergic neurons. Irrespective of the gender, however, both steroids decreased DA and DOPAC contents in diencephalic cultures but not in mesencephalic cultures. It is proposed that sexual differentiation of dopaminergic systems proceeds in a region-specific fashion and that neurogenesis and development of various parameters of dopaminergic activity may be differentially affected. Sexual differentiation of dopaminergic neurons may be initiated independently of the action of gonadal steroid hormones and may subsequently be modified by differences in hormonal environment.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Does the gender relevance of the stressor influence sex differences in psychophysiological responses?

Sex differences in psychophysiological responses to stress may be important to understanding sex differences in risk for coronary heart disease. This investigation tested the hypothesis that the gender relevance of the stressor influences the extent of sex differences in cardiovascular, neuroendocrine, and lipid responses during stress. Participants performed two tasks that were described as masculine oriented, feminine oriented, or not gender relevant. Although these descriptions influenced the participants' perceptions of the tasks, they did not influence the extent of sex differences in physiological responses in a manner consistent with the study hypothesis. Future directions for research are discussed regarding sex differences in psychophysiological responses.

Achievement↗
PubMed1998

Sex differences in discriminative stimulus and diuretic effects of the kappa opioid agonist U69,593 in the rat.

Female and male rats were trained to discriminate the kappa opioid agonist (5alpha,7alpha,8beta)-(-)-N-methyl-[7-(1-pyrrolidinyl) -1-oxaspiro(4,5)dec-8-yl]benzeneacetamide (U69,593, 0.13 mg/kg SC) from vehicle using a FR-10 schedule of food reinforcement. Female rats took significantly longer than males to acquire the discrimination (66.9 vs. 44.1 sessions, respectively), and the ED50 for U69,593 discrimination was significantly higher in females than in males (0.074 vs. 0.025 mg/kg). The time course of U69,593 discrimination also differed between the sexes: peak and offset occurred earlier in females than in males. The ED50 for bremazocine substitution was significantly higher in females than in males (0.0039 vs. 0.0006 mg/kg), whereas ethylketazocine substituted for U69,593 in all males and five of seven females, with no sex difference in substitution ED50. Morphine and BW373U86 did not substitute for U69,593 in a majority of rats of either sex. U69,593 also produced significantly less urine output/dose in females compared to males (e.g., 5.92 vs. 14.83 ml urine/kg body weight after 1.0 mg/kg U69,593), but was equipotent between the sexes in producing hot-plate antinociception. There was no sex difference in response rate-decreasing effect of any opioid agonist tested, and no sex difference in brain/blood ratio of [3H]U69,593 measured in a separate group of rats, suggesting that sex differences observed in some effects of U69,593 probably are not due to sex differences in U69,593 pharmacokinetics. When retested at the end of the study, U69,593 and bremazocine were no longer differentially potent as discriminative stimuli in females and males, suggesting that factors that change over time (e.g., additional training, age, hormonal status) may contribute to initial sex differences in discriminability of U69,593.

Animals↗
PubMed1991

[Sex differences in schizophrenic diseases].

Sex differences in schizophrenic diseases have been known for a long time but have also been subject to long-term neglect by psychiatric epidemiological research, although a study of these sex differences could, in our opinion, yield valuable pointers to pathogenic factors involved in this group of diseases the aetiology of which still awaits clarification. For this reason we initiated large-scale investigations focussed on this topic. The paper presented here discusses a few initial results, basing on data of Mannheim and National Danish Case Records and on our own study on schizophrenia, the latter being a representative record of 392 patients hospitalised for the first time in the Rhine-Neckar region and the eastern part of the Palatinate. First of all, sex differences at the age at which the disease appeared for the first time, were studied while paying close attention to artifacts and other, usually neglected methodical error sources. The difference in the average age of the sexes at first hospitalisation was confirmed, and also--using an instrument specially developed for that purpose--at the onset of the disease. At the time the first signs of the disease are noticed and the first schizophrenic symptoms become apparent, men are about 3 to 4 years younger than women. On the other hand, the cumulative lifetime risk--calculated up to 60 years of age--seems to be the same for both sexes. It appears that there are no sex differences in the pattern of symptoms of the disease at the time of initial hospital admittance, in respect of both the most common and the characteristic signs and symptoms. There were significant although quantitatively not very great differences in respect of patient behaviour which displays socially positive aspects somewhat more often in women and socially negative ones distinctly more often in men. In respect of the course of the disease we could not find any marked sex differences over a period of 10 years after onset of the disease; however, this is presently based only on the Danish case record data and on criteria of the course of the disease, such as number and duration of inpatient treatments.

Adolescent↗