Sex differences and sex hormones in experimental liver injury.
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Contribution of sex differences in the acute stress response to sex differences in water maze performance in the rat.
Male rats outperform females in spatial tasks, such as the water maze (WM). Female rats are known to have higher basal serum corticosterone (CORT) levels and to manifest a more rapid and stronger CORT response to novel stressors. Sex differences in stress responses to the handling and forced swimming in the WM task might contribute to the sex difference in WM performance. In Experiment 1, naive females were found to be impaired relative to naive males in swimming to a visible platform in a WM pool due to strongly thigmotaxic swimming by females. In Experiment 2, serum CORT, a physiological measure of stress, was highly elevated during and after WM training, with female > male values and strong inverse correlations between CORT and measures of WM performance in females. Familiarization with the WM pool and test procedures by strategies pretraining prior to spatial training reduced or eliminated the sex differences in the stress response and WM performance. In Experiment 3, adrenalectomy to eliminate the stress response eliminated sex differences in WM performance. Taken together, the results suggest that male and female rats may harbor brain circuitry that is equally capable of accurate spatial navigation and memory in the WM but which may be impaired to different degrees by the differential stress responses triggered by WM testing.
Adrenalectomy↗
Sex differences in cortisol secretion after administration of an ACTH analogue in sheep during the breeding and non-breeding season.
The aim of this study was to compare the response of cortisol in sheep of different sex and gonadal status to adrenal cortex stimulation by an ACTH analogue in the breeding and non-breeding season. Twenty-four adult Corriedale sheep were used in the non-breeding season, and 19 in the breeding season. Three weeks prior to the first trial (non-breeding season), six rams and six ewes were gonadectomised. In each trial, blood was obtained every 15min for 9h and the animals received 0.5mg of ACTH (Tetracosactid, Synacthen Depot i.m., after 1.5h of sampling. Sampling began at 10:00a.m. in the non-breeding season and at 9:00a.m. in the breeding season. Three main effects (sex, gonadal status and season) were evaluated, each with two levels (male and female, intact and gonadectomised, breeding and non-breeding season, respectively). In both seasons, the females showed higher cortisol levels after ACTH than males (P<0.001), though the difference seemed less marked in the non-breeding season. The cortisol response in the ewes was not affected by season. The rams, however, showed a lower response in the breeding season (P<0.03). Gonadectomy reduced the response in the ewes (P<0.001) but had no effect in the rams. Nevertheless, gonadectomy also eliminated the differences between the ewes and the rams, such that the intact rams had lower levels of cortisol compared to the intact females, with those of the gonadectomised animals of both sexes being intermediate between the gonad-intact groups. The results of this study confirm sex differences in ACTH induced cortisol secretion in intact sheep in vivo. Furthermore, by applying exogenous ACTH we have directly stimulated the adrenal cortex, indicating the existence of sex differences also at this level. The circulating gonadal steroids, which are responsible at least in part for the sex differences in the responses to stress, may influence cortisol secretion from the adrenal gland by direct action at the cortex.
Adrenal Cortex↗
Maternal investment. Sex differences in avian yolk hormone levels.
It has been suggested that female birds put more resources into eggs fathered by attractive males by laying larger eggs or by adding more testosterone, but this inference could be undermined if eggs of different sex are provisioned differently, as these studies did not control for sex differences. Here we compare hormone concentrations in the yolks of male and female eggs and find that these are significantly different. Our results indicate that it is premature to conclude that female birds invest more in eggs sired by a preferred male, and raise the possibility that yolk sex steroids may be part of the sex-determining process in birds.
Animals↗
Sex difference in free erythrocyte protoporphyrin (FEP) level. IV. Sex difference in FEP level in rabbits exposed to lead.
An experimental study on Japanese White (JW) rabbits was conducted to clarify the sex difference in FEP level. Male and female rabbits (n = 14 of each sex) were used. The animals of the same sex were divided into 3 groups; i.e., control group (5% glucose solution only, n = 4), low lead dose group (Pb 0.4 mg/kg.BW, n = 5) and high lead dose group (Pb 2 mg/kg.BW, n = 5). Lead was injected intravenously twice a week for 5 wk. The following parameters were determined once a week for 5 wk: blood lead (Pb-B), FEP, Ht, Hb, erythrocyte ALA-D activity, erythrocyte pyrimidine 5'-nucleotidase (P5N), urinary coproporphyrin (CP-U), urinary delta-aminolevulinic acid (ALA-U), iron in serum (Fe-S), and serum GOT and GTP. Average levels of FEP in female rabbits were higher than those in males between the 1st and 3rd week after the lead injection in the low lead dose groups, and in the final week in the high lead dose groups. In the periods without lead injection, the average levels of FEP in the female groups were not significantly higher than the corresponding levels in the male groups in every week except in the first week in the control. However, the mean of FEP levels in all female rabbits without Pb treatment was higher than that in male rabbits (t-test). By the analysis of variance for the gains of FEP from the initial value, only the low lead dose group showed a significant sex difference (female > male); that is, the female group tended to increase when compared with the male group. Furthermore, the week when FEP began to increase in the female groups was earlier than that in the male groups in the low lead dose group. In the high lead dose group, both sexes reacted to the lead exposure from the same early week. As for the parameters of anemia, the average levels of Ht and Hb tended to be lower in females than in males, but Fe-S levels were not affected by lead in both sexes and no consistent sex difference could be observed. By lead exposure, ALA-D and P5N were inhibited, and ALA-U was increased, but these parameters showed no evident sex difference. The average levels of CP-U tended to be higher in females than in males in the administration of low lead dose and to be inversely higher in males than in females in the administration of high lead dose.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
[Sex difference in free erythrocyte protoporphyrin (FEP) level. II. Sex difference in FEP level in rats exposed to lead].
An experimental study on Donryu rats was primarily carried out to elucidate sex difference in FEP level. Each of 33 male and 33 female rats was divided into 3 groups; that is, control group (5% glucose solution only), low lead dose group (Pb 0.5 mg/kg.BW) and high lead dose group (Pb 5 mg/kg.BW). Lead was injected intraperitoneally once a week for 6 wk. FEP, Ht, urinary coproporphyrin (CP-U), delta-aminolevulinic acid (ALA-U) and porphobilinogen (PBG-U) were determined once every two weeks for 6 wk, and whole blood lead (Pb-B) at the end of the experiment. Mean value of Ht was lower in females than in males throughout the period of the experiment in almost all groups. Pb-B level of all groups and erythrocyte Pb level of high dose group were higher in males than in females. FEP level without lead injection and with low lead exposure was higher in males than in females. By analysis of variance for gain from initial FEP level, only the low lead dose group demonstrated a significant sex difference (p less than 0.01); the female group tended to increase, while the male group maintained a constant level. Furthermore, FEP/Pb-B ratio in females was higher than in males only for the high dose group. The changes in ALA-U in male and female rats were comparable to those in FEP. Unlike FEP and ALA-U, CP-U level was higher in males than in females only for the high lead dose group. In this study using rats, sex difference in FEP level was different from that in human.(ABSTRACT TRUNCATED AT 250 WORDS)
Aminolevulinic Acid↗
Sex differences in chiasma distribution along two marked mouse chromosomes: differences in chiasma distribution as a reason for sex differences in recombination frequency.
Chiasma distributions along bivalents 1 and 14 in female and male mice were studied. It was shown that the average chiasma number in both chromosomes show no sex difference. There are however, significant sex differences in chiasma distribution along 1 and 14 chromosomes. In males there are two terminal chiasma peaks in chromosome 1 and one subtelomeric peak of chiasmata in chromosome 14. In females chiasma distributions are more even. According to genetic data, females produce more recombinants between loci of chromosome 1 than males do. By means of a computer simulation it was demonstrated that the differences in the average recombination frequency result from differences in chiasma distribution.
Animals↗
Are sex differences in child motor activity level a function of sex differences in maturational status?
By virtue of being farther along a developmental path for motor activity level, girls may appear to be the less active sex when compared to less physically mature but same-aged boys. If so, observed sex differences in activity level may be an epiphenomenon of sex differences in maturity related declines in AL. To test this hypothesis and the associated premise that females would be more mature and less active than males, the customary activity levels and relative physical maturities of 83 5-8-year-olds were assessed. Relative maturity (percentage of estimated adult height attained) was negatively related to activity level, and girls were both less motorically active and more mature than boys. Though reduced in magnitude, the sex effect remained significant after maturity was added as a predictor of AL. Thus, sex differences are not due only to maturity differences but may be partially mediated by them.
Age Factors↗
The preoptic area/anterior hypothalamus of different strains of mice: sex differences and development.
While sex differences in neural morphology in the preoptic area/anterior hypothalamus (POA/AH) have been demonstrated in many species, their existence in mice have been controversial. Given the increased use of transgenic and gene-disrupted mice, we characterized sex differences using Nissl stains, and the immunocytochemical location of estrogen receptor-alpha (ER-alpha) and galanin in the POA/AH of two widely used strains, C57BL/6 and 129SvEv, and a mixed strain (C57BL/6x129Sv); the wild-type littermates of steroidogenic factor-1 (SF-1) gene-disrupted mice. Cell grouping was not a reliable marker of sex. In adults, cells located beneath the anterior commissure (AC) were reliably larger in females than males in 129SvEv, but not in the other strains. Caudally, cells in a group medial to the medial extension of the bed nucleus of the stria terminalis (BST) were significantly larger in males than females in C57BL/6J and SF-1 gene-disrupted wild-types. Cell groups discernible by embryonic day (E) 18 were not sexually dimorphic for cell size in C57BL/6J mice at E18 or postnatal day (P) 4. The pattern of distribution of cells containing ER-alpha was similar among the strains, reduced in the group medial to the BST; a pattern established by P0. Galanin-containing cells and fibers were seen from E15 to adulthood ventral to the AC. Caudally, a smaller group ventromedial to the BST was found only in 129SvEv adults. Sex differences in neural morphology which develop within the POA/AH depend upon multiple factors, particularly including genetic background.
Animals↗
Sex differences in oestrogen receptor levels in adrenal glands of sheep during the breeding season.
The concentrations of the oestrogen receptor (ER), and the mRNA levels of ERalpha, progesterone receptor (PR) and insulin-like growth factor I (IGF-I) were characterised in adrenal glands and uterine tissue of adult Corriedale sheep during the breeding season. The sheep were of different sex and gonadal status. Ewes had higher levels of cytosolic ER in the adrenals than the rams (mean+/-S.E.M.: 7.3+/-2.0 fmol/mg protein and 2.5+/-1.0 fmol/mg protein, respectively; P=0.0091) and gonadectomy increased ER (mean+/-S.E.M.: 2.9+/-1.2 fmol/mg protein and 8.6+/-2.3 fmol/mg protein, intact and gonadectomised sheep, respectively; P=0.0071). No differences could be observed in mRNA levels for ERalpha and IGF-I in the adrenal glands of all of the sheep. PR mRNA levels were reduced in ovariectomised ewes and enhanced in castrated rams (sex x gonadal status: P=0.009). PR mRNA levels tended to be higher in ewes in the follicular phase than in ovariectomised ewes and intact rams (P<0.1). All of the animals had positive nuclear staining for ERalpha in the adrenal cortex, but no differences were observed between the groups. In this study, we demonstrated the existence of ER in the adrenal gland of sheep and found varying sensitivity to oestrogens as the ER levels differed among sex and gonadal status. These findings indicate that oestrogens most likely affect steroidogenesis directly at the adrenal cortex and suggest that oestrogens are partly responsible for the sex differences in cortisol secretion in sheep.
Adrenal Glands↗
[Sex difference in free erythrocyte protoporphyrin (FEP) level. I. Sex difference in FEP level in healthy rural residents].
FEP and other hematological parameters were measured in 157 healthy rural residents (98 females and 59 males). The mean FEP in females was higher than in males (p less than 0.05); mean +/- SD = 62.98 +/- 19.36 and 54.57 +/- 21.20 micrograms/dl.pcv, respectively, although both of the means were within normal limits. There was no significant sex difference in erythrocyte ALA-D activity. Whole blood lead (Pb-B) level in females showed a tendency to be lower than in males, but there was no significant sex difference in erythrocyte lead level. The mean value of hematocrit (Ht), hemoglobin (Hb) and iron in serum (Fe-S) were lower in females than in males (p less than 0.01). Serum GOT and GPT level tended to be lower in females than in males (0.05 less than p less than 0.1). There was hardly any significant relationship between Pb-B and each parameter of lead exposure, because the subjects in this study were only rural residents with no occupational lead exposure and with their Pb-B levels being extremely low. As for the parameters of anemia, Fe-S was positively correlated with Ht and Hb level and negatively correlated with FEP level. By sex, Fe-S was correlated with Ht and FEP level only in females. As for the possible reasons why FEP level in females in higher than in male, women tended to have iron-deficiency induced by blood loss due to menstruation, pregnancy, and difference in dietary pattern from males.
Adult↗
Sex differences in interaction style as a product of perceived sex differences in competence.
Males' and females' interaction styles were observed while they worked in four-person, mixed-sex groups on a discussion task. In some groups, members were only given information about each others' names and gender. In this circumstance, men were perceived by themselves and other group members to be higher in competence than women. Further, men engaged in a greater amount of active task behavior than women (e.g., giving information, giving opinions), and women exhibited a greater amount of positive social behavior than men (e.g., agreeing, acting friendly). In other groups, members' competency-based status was manipulated by providing false feedback that they were high or low relative to their group in intellectual and moral aptitude. High status members were then perceived to be more competent than low status ones and, further, high status individuals engaged in more active task and less positive social behavior than low status ones. In this condition, no sex differences were obtained on perceived competence or on active task or positive social behavior. Overall, these findings support the idea that the gender differences obtained in interaction when status was not specified were partially a function of group members' belief that the sexes differ in competence. Direct information concerning members' intellectual and moral competence apparently blocked the perceived gender-to-competence link, and status alone affected perceived competence and interaction style.
Achievement↗
Bateman's principle and immunity: phenotypically plastic reproductive strategies predict changes in immunological sex differences.
The sexes often differ in the reproductive trait limiting their fitness, an observation known as Bateman's principle. In many species, females are limited by their ability to produce eggs while males are limited by their ability to compete for and successfully fertilize those eggs. As well as promoting the evolution of sex-specific reproductive strategies, this difference may promote sex differences in other life-history traits due to their correlated effects. Sex differences in disease susceptibility and immune function are common. Two hypotheses based on Bateman's principle have been proposed to explain this pattern: that selection to prolong the period of egg production favors improved immune function in females, or that the expression of secondary sexual characteristics reduces immune function in males. Both hypotheses predict a relatively fixed pattern of reduced male immune function, at least in sexually mature individuals. An alternative hypothesis is that Bateman's principle does not dictate fixed patterns of reproductive investment, but favors phenotypically plastic reproductive strategies with males and females adaptively responding to variation in fitness-limiting resource availability. Under this hypothesis, neither sex is expected to possess intrinsically superior immune function, and immunological sex differences may vary in different environments. We demonstrate that sex-specific responses to experimental manipulation of fitness-limiting resources affects both the magnitude and direction of sex differences in immune function in Drosophila melanogaster. In the absence of sexual interactions and given abundant food, the immune function of adults was maximized in both sexes and there was no sex difference. Manipulation of food availability and sexual activity resulted in female-biased immune suppression when food was limited, and male-biased immune suppression when sexual activity was high and food was abundant. The immunological cost to males of increased sexual activity was found to be due in part to reduced time spent feeding. We suggest that for species similarly limited in their reproduction, phenotypic plasticity will be an important determinant of sex differences in immune function and other life-history traits.
Adaptation, Physiological↗
Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis.
CONTEXT: Inconsistent data suggest that endogenous sex hormones may have a role in sex-dependent etiologies of type 2 diabetes, such that hyperandrogenism may increase risk in women while decreasing risk in men. OBJECTIVE: To systematically assess studies evaluating the association of plasma levels of testosterone, sex hormone-binding globulin (SHBG), and estradiol with risk of type 2 diabetes. DATA SOURCES: Systematic search of EMBASE and MEDLINE (1966-June 2005) for English-language articles using the keywords diabetes, testosterone, sex-hormone-binding-globulin, and estradiol; references of retrieved articles; and direct author contact. STUDY SELECTION: From 80 retrieved articles, 43 prospective and cross-sectional studies were identified, comprising 6974 women and 6427 men and presenting relative risks (RRs) or hormone levels for cases and controls. DATA EXTRACTION: Information on study design, participant characteristics, hormone levels, and risk estimates were independently extracted by 2 investigators using a standardized protocol. DATA SYNTHESIS: Results were pooled using random effects and meta-regressions. Cross-sectional studies indicated that testosterone level was significantly lower in men with type 2 diabetes (mean difference, -76.6 ng/dL; 95% confidence interval [CI], -99.4 to -53.6) and higher in women with type 2 diabetes compared with controls (mean difference, 6.1 ng/dL; 95% CI, 2.3 to 10.1) (P<.001 for sex difference). Similarly, prospective studies showed that men with higher testosterone levels (range, 449.6-605.2 ng/dL) had a 42% lower risk of type 2 diabetes (RR, 0.58; 95% CI, 0.39 to 0.87), while there was suggestion that testosterone increased risk in women (P = .06 for sex difference). Cross-sectional and prospective studies both found that SHBG was more protective in women than in men (P< or =.01 for sex difference for both), with prospective studies indicating that women with higher SHBG levels (>60 vs < or =60 nmol/L) had an 80% lower risk of type 2 diabetes (RR, 0.20; 95% CI, 0.12 to 0.30), while men with higher SHBG levels (>28.3 vs < or =28.3 nmol/L) had a 52% lower risk (RR, 0.48; 95% CI, 0.33 to 0.69). Estradiol levels were elevated among men and postmenopausal women with diabetes compared with controls (P = .007). CONCLUSIONS: This systematic review indicates that endogenous sex hormones may differentially modulate glycemic status and risk of type 2 diabetes in men and women. High testosterone levels are associated with higher risk of type 2 diabetes in women but with lower risk in men; the inverse association of SHBG with risk was stronger in women than in men.
Diabetes Mellitus, Type 2↗
Selective breeding for differences in cholinergic function: sex differences in the genetic regulation of sensitivity to the anticholinesterase, DFP.
Genetic factors involved in the sensitivity of behavioral and physiological variables to the anticholinesterase diisopropyl fluorophosphate (DFP) were studied by comparing the sensitivities to DFP of two lines of rats selectively bred to be either sensitive ( Flinders S-line) or resistant ( Flinders R-line) with F1 and F2 genetic crosses between the two lines. The dependent variables selected were body weight, core body temperature, and water intake. Statistical analyses with two-way ANOVA revealed highly significant line differences for all variables and significant sex differences for core body temperature and water intake. Among the lines and crosses the S-line was more sensitive, followed in order by the F2, F1 and R-line. However, the relative differences among the lines varied for the two sexes. The F1 males were almost identical to their R-line counterparts, whereas F1 females were intermediate between the female S- and R-lines. The data were also subjected to discriminant function analyses and similar relationships were found. Estimates of the number of genes involved in the inheritance of DFP sensitivity suggest a single gene in males and two genes in females. The data for the males were reasonably consistent with a model for a single recessive gene coding for DFP sensitivity. On the other hand, the data for the females could be fitted better with a two-gene model, although there was not a complete fit with the observed data. These results provide strong support for sex differences in the genetic regulation of DFP sensitivity.
Animals↗
Evaluation of sex differences on mitochondrial bioenergetics and apoptosis in mice.
It has been postulated that the differences in longevity observed between organisms of different sexes within a species can be attributed to differences in oxidative stress. It is generally accepted that differences are due to the higher female estrogen levels. However, in some species males live the same or longer despite their lower estrogen values. Therefore, in the present study, we analyze key parameters of mitochondrial bioenergetics, oxidative stress and apoptosis in the B6 (C57Bl/6J) mouse strain. There are no differences in longevity between males and females in this mouse strain, although estrogen levels are higher in females. We did not find any differences in heart, skeletal muscle and liver mitochondrial oxygen consumption (State 3 and State 4) and ATP content between male and female mice. Moreover, mitochondrial H(2)O(2) generation and oxidative stress levels determined by cytosolic protein carbonyls and concentration of 8-hydroxy-2'-deoxyguanosine in mitochondrial DNA were similar in both sexes. In addition, markers of apoptosis (caspase-3, caspase-9 and mono- and oligonucleosomes: the apoptosis index) were not different between male and female mice. These data show that there are no differences in mitochondrial bioenergetics, oxidative stress and apoptosis due to gender in this mouse strain according with the lack of differences in longevity. These results support the Mitochondrial Free Radical Theory of Aging, and indicate that oxidative stress generation independent of estrogen levels determines aging rate.
Animals↗
The relationship in African-Americans of sex differences in insulin-mediated suppression of nonesterified fatty acids to sex differences in fasting triglyceride levels.
Insulin is a potent antilipolytic hormone that promotes the deposition of fat and decreases the release of nonesterified fatty acids (NEFA) from adipose tissue. The purpose of this study was to investigate in African-Americans (AAs) sex differences in insulin-mediated suppression of plasma NEFA and fasting triglyceride (TG) levels. Ninety AAs, 44 men and 46 women with a mean age of 34 +/- 8 years were classified by body mass index (BMI) into three groups: non-obese (22 men and 18 women), obese (12 men and 10 women), and severely obese (10 men and 18 women). In each BMI group, women versus men had greater percent body fat (non-obese, 30 +/- 6 v 18 +/- 6, P < .001; obese, 36 +/- 3 v 26 +/- 2, P < .001; and severely obese, 39 +/- 4 v 29 +/- 4, P < .001). An oral glucose tolerance test (OGTT) was performed with fasting TG levels and plasma insulin and NEFA concentrations obtained at 0, 30, 60, and 120 minutes. In women, insulin-mediated NEFA suppression was similar in each of the three BMI groups (non-obese, 85% +/- 14%; obese, 88% +/- 11%; and severely obese, 87% +/- 10%; P = .8). In men, the percent suppression of NEFA declined with increasing obesity (non-obese, 83% +/- 14%; obese, 71% +/- 21%; and severely obese, 68% +/- 16%; P = .04). Changes in NEFA suppression were reflected in the fasting TG levels. TG levels in women were similar in each BMI group (non-obese, 71 +/- 39 mg/dL; obese; 69 +/- 21; severely obese, 79 +/- 30; P = .7). In contrast, fasting TG levels for men were higher in the higher BMI groups. Plasma TG levels in men were 87 +/- 41 mg/dL for obese, 113 +/- 65 for obese, and 169 +/- 81 for severely obese (P = .001). These data demonstrate sex differences in insulin-mediated NEFA metabolism. In AA women, the maintenance of sensitivity to insulin-mediated suppression of NEFA regardless of the degree of obesity may contribute to the normal plasma TG levels. For AA men, the resistance to insulin-mediated suppression of NEFA in the higher BMI categories may allow more NEFA to be released from adipose tissue into the circulation and available to the liver for synthesis into TG-containing lipoproteins.
Adult↗
[Lipid metabolism of neonatally thymectomized rats of different sexes].
Content of cholesterol, its esters, total beta-lipoproteins and free fatty acids was increased in blood serum of rats, subjected to thymectomia after birth. The distinct sex variations were found in alterations of these patterns. Content of cholesterol was increased only in thymectomized males at the age of 3 months; content of beta-lipoproteins in males was elevated earlier and to higher level as compared wtih females. Alteration in content of blood serum lipids did not depend on manifestations of exhaustion syndrome (typical consequence of neonatal thymectomia) but it was related to ablation of thymus; this suggests that thymus participates in regulation of lipid metabolism. Sex differences in alterations of lipid metabolism patterns enabled to assume the existence of endocrine interrelations between thymus and sex glands.
Animals↗