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Sex difference in serum 7 alpha-hydroxycholesterol levels in the rat reflect hepatic activity of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase and cholesterol 7 alpha-hydroxylase.

Factors that affect serum levels of 7 alpha-hydroxycholesterol were studied in the rat. Serum levels of 7 alpha-hydroxycholesterol differed in male and female rats fed regular chow (male; 0.2 +/- 0.1 nmol/ml (mean +/- SD); n = 8; female; 0.4 +/- 0.1 nmol/ml; n = 8). When rats were fed with chow to which 3% cholestyramine had been added, the level increased significantly, particularly in female rats (male; 0.6 +/- 0.3 nmol/ml; n = 8; female; 2.4 +/- 1.5 nmol/ml; n = 8). The liver activity of cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme for degradation of cholesterol, did not show any sex differences, irrespective of whether the animals were fed with regular chow (male; 51 +/- 15 pmol/min per mg protein; n = 8; female; 58 +/- 21 pmol/min per mg protein; n = 8), or the cholestyramine-supplemented chow (male; 162 +/- 33 pmol/min per mg protein; n = 8; female; 172 +/- 33 pmol/min per mg protein; n = 8). In contrast, the activity of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase, which acts after cholesterol 7 alpha-hydroxylase in the catabolism of cholesterol, showed a marked difference between the sexes. In both sexes this enzyme activity was higher in cholestyramine-treated rats (male; 963 +/- 78 pmol/min per mg protein; n = 8; female; 708 +/- 106 pmol/min per mg protein, n = 8) compared to that in that rats received regular chow (male; 622 +/- 83 pmol/min per mg protein; n = 8; female; 469 +/- 41 pmol/min per mg protein; n = 8). If the serum level of 7 alpha-hydroxycholesterol depended solely on the enzyme activity of cholesterol 7 alpha-hydroxylase, it would be difficult to explain these sex differences, since there were no sex differences in levels of cholesterol 7 alpha-hydroxylase. These results clearly indicate that, in the rat, the serum level of 7 alpha-hydroxycholesterol depends not only on cholesterol 7 alpha-hydroxylase activity but also on 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase activity.

3-Hydroxysteroid Dehydrogenases↗

Sex differences in opioid antinociception: kappa and 'mixed action' agonists.

A number of investigators have shown that male animals are more sensitive than females to the antinociceptive effects of mu-opioid agonists. The present study was conducted to examine sex differences in opioid antinociception in the rat using agonists known to differ in selectivity for and efficacy at kappa- versus mu-receptors. Dose- and time-effect curves were obtained for s.c. U69593, U50488, ethylketazocine, (-)-bremazocine, (-)-pentazocine, butorphanol and nalbuphine on the 50 or 54 degrees C hotplate and warm water tail withdrawal assays; spontaneous locomotor activity was measured 32-52 min post-injection in the same rats. On the hotplate assay, only butorphanol (54 degrees C) and nalbuphine (50 degrees C) were significantly more potent in males than females. On the tail withdrawal assay, all agonists were significantly more potent or efficacious in males than females at one or both temperatures. In contrast, no agonist was consistently more potent in one sex or the other in decreasing locomotor activity. Estrous stage in female rats only slightly influenced opioid effects, accounting for an average of 2.6% of the variance in females' antinociceptive and locomotor responses to drug (50 degrees C experiment). These results suggest that (1) sex differences in antinociceptive effects of opioids are not mu-receptor-dependent, as they may occur with opioids known to have significant kappa-receptor-mediated activity; (2) the mechanisms underlying sex differences in kappa-opioid antinociception may be primarily spinal rather than supraspinal; (3) sex differences in antinociceptive effects of opioid agonists are not secondary to sex differences in their sedative effects.

Adaptation, Physiological↗

Cerebral asymmetry in autonomic conditioning to facial expressions: sex differences.

In the present experiment, sex differences in hemispheric asymmetry during classical conditioning to emotional stimuli are reported. 125 subjects (62 females and 63 males) were shown a slide of a happy face in the right (or left) visual half field (VHF), and simultaneously a slide of an angry face in the left (or right) VHF. Eight groups were formed by the combination of male and female subjects; left and right VHF positions of the angry/happy faces; and the administration/omission of the shock unconditioned stimulus (UCS). Dependent measures were skin conductance responses recorded from both hands. The results during extinction showed a significant larger SCR magnitude to the shock compared to the no-shock groups only for the female subjects. CS position during conditioning was also important in revealing differential responding to either the happy or angry faces. A right hemisphere effect was found for the angry face CS for both the male and female subjects, however with a greater difference for the females.

Adolescent↗

Sex differences in cognitive functioning in velocardiofacial syndrome (VCFS).

Sex differences in cognitive functioning were investigated in children with velocardiofacial syndrome (VCFS), a genetic defect caused by a microdeletion on chromosome 22q.11. The study population consisted of six groups: 50 boys with VCFS (M = 11.1, SD = 2.7), 40 girls with VCFS (M = 10.8, SD = 2.5), 13 male siblings of the participant with VCFS (M = 12.3, SD = 1.9), 17 female siblings of the participant with VCFS (M = 12.2, SD = 1.9), and a race- and gender-ratio-matched sample of 28 boy community control participants (M = 10.7, SD =2.4) and 19 girl community control participants (M = 9.2, SD =2.3). Each participant received a psychological assessment including intellectual and academic achievement as well as structural magnetic resonance imaging of his or her brain. Our results indicate that boys with VCFS may be more cognitively affected than girls. In addition, and although cross-sectional in nature, our results document a negative association between age and cognitive functioning in girls with VCFS but not in boys. Sex differences in frontal lobe volume are generally seen in the general population between boys and girls (boys > girls) and across all three samples, this trend emerged. Relative to boys with VCFS, girls with VCFS may be less cognitively affected, although age is negatively associated with cognitive functioning in girls with VCFS but not boys, suggesting that girls with VCFS may fail to maintain this cognitive advantage over boys.

Adolescent↗

Proteome analysis provides insights into sex differences in Holothuria Scabra.

Sex-determining mechanism is still ambiguous for sea cucumber Holothuria scabra which only manifests gonochorism in gonad. In this study, proteomic analysis was employed to delineate sex-related proteins and genes in gonads of H. scabra, subsequently validated through Quantitative real-time polymerase chain reaction (qRT-PCR). A total of 5,313 proteins were identified via proteome sequencing. Among these, 817 proteins exhibited expression in both the ovary and testis, with 445 proteins displaying up-regulation and 372 proteins showing down-regulation (ovary vs testis). Furthermore, 136 and 69 proteins were identified as ovary-specific and testis-specific Differentially Abundant Proteins (DAPs), respectively. And 9 DAP coding genes which play crucial role in ovary and testis were verified by qRT-PCR. Notably, 24 ovary-bias proteins enriched in ribosome pathway strongly indicated the crucial role of ribosome in ovary. This study serves to furnish novel evidence pertaining to sex differences in H. scabra.

Animals↗

Sex differences in righting from supine to prone in rats (Rattus norvegicus): a masculinized skeletomusculature is not required.

Previous research has shown that sex differences exist in the composition of lateral movements (E. F. Field, I. Q. Whishaw, & S. M. Pellis, 1996, 1997a, 1997b; see also records 1996-06132-009, 1997-05322-015, and 1997-04722-005). An unresolved question is whether sex differences are present in other movements, such as rotation around the longitudinal axis, and whether this difference is dependent on a feminine or masculine skeletomusculature. Female rats (Rattus norvegicus) first rotate their forequarters and then their hindquarters in the same direction. Male rats exhibit rotation of the hindquarters counter to the direction of forequarter rotation. Males with the testicular feminized mutation, who have a feminized skeletomusculature and masculinized central nervous system, are similar to male controls. This study provides evidence that sex differences in movement integration are not restricted to the lateral plane, are not solely due to sex differences in skeletomusculature, and thus are likely mediated by the central nervous system.

Animals↗

Contribution of sensory neurons to sex difference in the development of stress-induced gastric mucosal injury in mice.

BACKGROUND & AIMS: Sensory neurons play a critical role in reducing stress-induced gastric mucosal injury by releasing calcitonin gene-related peptide (CGRP) through an increase in gastric mucosal levels of prostacyclin (PGI(2)). Because estrogen enhances nerve growth factor-mediated CGRP production in sensory neurons, we hypothesized that stress-induced gastric mucosal injury occurs less in females than in males. METHODS: Gastric ulcer index, gastric myeloperoxidase activity, and gastric tissue levels of CGRP and 6-keto-PGF(1alpha), a stable metabolite of PGI(2), were determined in male and female wild-type (CGRP(+/+)) mice and CGRP knockout (CGRP(-/-)) mice subjected to water-immersion restraint stress. RESULTS: In CGRP(+/+) mice, ulcer index and myeloperoxidase activities were lower and gastric tissue levels of CGRP and 6-keto-PGF(1alpha) were higher in female mice than in male mice, but there were no such sex differences in CGRP(-/-)mice. Sex differences in CGRP(+/+) mice were eliminated by pretreatment with SB366791 (500 microg/kg intraperitoneally), a vanilloid receptor antagonist, and by ovariectomy. Reversal of sex differences by ovariectomy was not observed in female CGRP(+/+) mice with estradiol replacement (1 mg . kg(-1). wk(-1) for 3 weeks). Levels of CGRP messenger RNA in dorsal root ganglion neurons isolated from female CGRP(+/+) mice were decreased by ovariectomy, and these decreases were reversed by estradiol replacement. CONCLUSIONS: Estrogen-mediated increases in CGRP levels in sensory neurons might contribute to reduce stress-induced gastric mucosal injury by attenuating inflammatory responses. This might at least partly explain the sex difference observed in the development of stress-induced gastric mucosal injury in mice.

Anilides↗

Functional sex differences ('sexual diergism') of central nervous system cholinergic systems, vasopressin, and hypothalamic-pituitary-adrenal axis activity in mammals: a selective review.

Sexual dimorphism of the mammalian central nervous system (CNS) has been widely documented. Morphological sex differences in brain areas underlie sex differences in function. To distinguish sex differences in physiological function from underlying sexual dimorphisms, we use the term, sexual diergism, to encompass differences in function between males and females. Whereas the influence of sex hormones on CNS morphological characteristics and function of the hypothalamic-pituitary-gonadal axis has been well-documented, little is known about sexual diergism of CNS control of the hypothalamic-pituitary-adrenal (HPA) axis. Many studies have been conducted on both men and women but have not reported comparisons between them, and many animal studies have used males or females, but not both. From a diergic standpoint, the CNS cholinergic system appears to be more responsive to stress and other stimuli in female than in male mammals; but from a dimorphic standpoint, it is anatomically larger, higher in cell density, and more stable with age in males than in females. Dimorphism often produces diergism, but age, hormones, environment and genetics contribute differentially. This review focuses on the sexual diergism of CNS cholinergic and vasopressinergic systems and their relationship to the HPA axis, with resulting implications for the study of behavior, disease, and therapeutics.

Acetylcholine↗

Cocaine-induced sex differences in D1 receptor activation and binding levels after acute cocaine administration.

Although it is established that female rats have a more robust behavioral response to acute cocaine administration than male rats, the neurobiological mechanisms underlying these differences remain unclear. The purpose of the present study was to determine whether dopamine (DA) receptor activation influences sex differences in cocaine-induced behaviors. A second study was performed to determine sex differences in D1/D2 receptor levels prior to and post-cocaine administration. Male and female Fischer rats were pre-treated with the D1 antagonist SCH-23390 (0.05, 0.1, and 0.25 mg/kg, i.p.), the D2 antagonist eticlopride (0.03, 0.1 mg/kg, i.p.), or vehicle (saline) 15 min before acute cocaine (20 mg/kg, i.p.) or saline administration. Cocaine-induced ambulatory and rearing activity was greater in female than male rats. Pre-treatment with SCH-23390 affected cocaine-induced ambulatory, rearing, and stereotypic activity in a sex-dependent manner; cocaine-induced ambulatory and stereotypic behavior in female rats was reduced by the lowest dose of SCH-23390. Eticlopride did not alter behavioral responses to cocaine in male or female rats. These results suggest that in both male and female rats, activation of the D1, but not the D2, receptor modulates cocaine's motor effects. There were no sex differences in baseline levels of D1, D2, and DA transporter binding in the caudate putamen (CPu) and the nucleus accumbens (NAc). Cocaine administration reduced D1 binding levels in the CPu only in male rats. Our findings suggest that the regulation of striatal D1 binding levels after acute cocaine administration is a sexually dimorphic process. We also hypothesize that the greater sensitivity to D1 receptor blockade in female rats, as compared to male rats, may contribute to their overall increased hyperactivity in response to acute cocaine. Taken together, the D1 receptor may be an important substrate in the regulation of sex differences to cocaine-induced locomotor activity.

Animals↗

Sex Differences in Mathematical Abilities: Commentary on the Math-Fact Retrieval Hypothesis.

The hypothesis that a male advantage in speed of math-fact retrieval underlies the sex difference, favoring males, in mathematical abilities is unique and provocative. However, the hypothesis does not provide an explanation for the male advantage in mathematical domains, such as geometry, that do not require arithmetic, nor does it accommodate the sex differences in social and occupational interests that contribute to the sex difference in mathematical achievement. An alternative hypothesis focusing on the sex difference in three-dimensional spatial cognition is favored over the math-fact retrieval hypothesis. Copyright 1999 Academic Press.

Journal Article↗

Female illness rates and illness behavior: testing hypotheses about sex differences in health.

Health surveys repeatedly show that females have higher rates of illness, disability days, and health services utilization than do males. Numerous reasons for these sex differences have been hypothesized, based on four general factors thought to differ by sex and to influence self-reported health: genetic characteristics, physical risks, illness behavior, and reporting behavior. This paper briefly reviews these hypotheses, then discusses research strategies to test them. The strategies vary in the type of dependent variables used (medical vs. sociomedical health indicators) and the main method of controlling predictor factors (elimination vs. statistical control). A study was completed in 1978 in the Detroit metropolitan area to (a) explore reasons for sex differences in health and (b) reveal how strongly illness behavior (perception and evaluation of symptoms, propensities to take curative actions or disability days) affects common health indicators, particularly those for the national Health Interview Survey. The study's research design (use of a health diary, and focus on hypotheses about illness behavior) is described.

Adult↗

Sex differences in clerical speed: perceptual speed versus comparison and decision speed.

The hypothesis that sex differences in clerical speed are based on differences in perceptual speed was tested in an experiment using tachistoscopic presentation of pairs of items requiring same-different judgments. This procedure eliminated the attentional shifts from item to item as well as the repetitive nature of the task. 10 females still were significantly faster than 10 males. Also no significant sex differences were found in an additional visual search task requiring rapid recognition and shifts in attention. Results were interpreted in terms of sex differences in comparison and decision time as opposed to perceptual speed.

Attention↗

Sex differences in visceral fat lipolysis and metabolic complications of obesity.

Cardiovascular complications of obesity are more common in men than women. Sex differences in visceral fat lipolysis may be of importance in this respect, since increased release of free fatty acids (FFAs) from visceral fat to the liver by the portal venous system has been thought to cause several metabolic complications due to obesity, such as hypertension, hyperlipidemia, and glucose intolerance. The aim of this study was to investigate sex differences in clinical characteristics and visceral fat mobilization in obesity. Obese subjects (22 male and 23 female) undergoing elective surgery were matched for body mass index and age. The males had both higher waist-to-hip ratio (WHR), sagittal diameter, blood pressure, fat-cell volume, plasma insulin, glucose, and triglyceride and lower HDL cholesterol levels than the females. The rate of norepinephrine-induced FFA and glycerol release was twofold higher in men (P = .02). No significant reutilization of FFA was observed. The difference in maximum norepinephrine-induced rate of lipolysis between men and women was independent of both WHR and sagittal diameter and was an independent regressor for levels of plasma glucose and plasma HDL cholesterol. Fat-cell volume was an independent regressor for plasma triglycerides and blood pressure. No sex differences in the lipolytic sensitivity to beta 1- or beta 2-adrenoceptor-specific agonists or in the antilipolytic effect of insulin were observed. However, the lipolytic beta 3-adrenoceptor sensitivity was 12 times higher (P = .004) and the antilipolytic alpha 2-adrenoceptor sensitivity 17 times lower (P = .003) in men. Furthermore, lipolysis induced by agents acting at the adenylate cyclase and protein kinase A levels were almost twofold enhanced in men. However, no sex difference in maximum hormone-sensitive lipase activity was observed. In conclusion, in obesity, catecholamine-induced rate of FFA mobilization from visceral fat to the portal venous system is higher in men than women. This phenomenon is partly due to a larger fat-cell volume but also to a decrease in the function of alpha 2-adrenoceptors, an increase in the function of beta 3-adrenoceptors, and an increased ability of cyclic AMP to activate hormone-sensitive lipase. These factors may contribute to gender-specific differences in metabolic and cardiovascular disturbances accompanied by obesity.

Adipose Tissue↗

Pharmacokinetic factors in sex differences in Delta 9-tetrahydrocannabinol-induced behavioral effects in rats.

Cannabinoids have been shown to produce greater behavioral effects in female than in male rats. Sex differences in the metabolism of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) have also been demonstrated in one study. The goal of this study was to determine if sex differences in Delta(9)-THC disposition or metabolism could explain sex differences in Delta(9)-THC-induced behavioral effects. [(3)H]-Delta(9)-THC was administered intraperitoneally (i.p.) to rats and the presence of [(3)H]-Delta(9)-THC and metabolites in serum and brain tissue were compared at multiple times post-injection in male versus female rats. Serum levels of Delta(9)-THC and its metabolites were similar in males and females. In brain tissue, [(3)H]-Delta(9)-THC levels also were similar in males and females. In contrast, levels of Delta(9)-THC metabolites in brain tissue, including 11-hydroxy-Delta(9)-THC, the major active metabolite, were higher in females than in males. To further investigate if greater production of active metabolites by females explained the greater Delta(9)-THC-induced behavioral effects observed in females, i.p. Delta(9)-THC-induced antinociception (50 degrees C warm water tail withdrawal assay) and catalepsy (bar test) were compared in male and female rats following pretreatment with saline or SKF525A, a cytochrome P450 inhibitor. SKF525A did not affect basal responding in the tail withdrawal assay or bar test in either sex. SKF525A significantly attenuated Delta(9)-THC-induced antinociception only in females. A similar sex difference was observed in the effects of SKF525A on Delta(9)-THC-induced catalepsy. These results suggest that the greater levels of active Delta(9)-THC metabolites produced by females contribute to greater behavioral effects of Delta(9)-THC in female compared to male rats.

Analgesics, Non-Narcotic↗

Sex differences in renal injury and nitric oxide production in renal wrap hypertension.

To investigate the faster rate of renal disease progression in men compared with women, we addressed the following questions in the renal wrap (RW) model of hypertension: 1) Do sex differences exist in RW-induced renal injury, which are independent of sex differences in blood pressure? 2) Do sex differences in nitric oxide (NO) production exist in RW hypertension? Male (M) and female (F) rats underwent sham-operated (M-Sham, n = 7; F-Sham, n = 10) or RW (M-RW, n = 13; F-RW, n = 14) surgery for 9 wk. Markers of renal injury, including the glomerulosclerosis index (F-RW, 0.70 +/- 0.1 vs. M-RW, 2.2 +/- 0.6; P < 0.05), mean glomerular volume (F-RW, 1.05 +/- 0.050 x 10(6) vs. M-RW, 1.78 +/- 0.15 x 10(6) microm(3); P < 0.001), and proteinuria (F-RW, 68.7 +/- 15 vs. M-RW, 124 +/- 7.7 mg/day; P < 0.001) were greater in RW males compared with RW females. Endothelial NO synthase protein expression was elevated in the renal cortex (3.2-fold) and medulla (2.2-fold) 9 wk after RW in males, whereas no differences were observed in females. Neuronal NO synthase protein expression was unchanged in the renal cortex in males and in both the renal cortex and medulla in females, whereas in the male medulla, neuronal NOS was decreased by 57%. These data suggest the degree of renal injury is greater in male compared with female rats in RW hypertension despite similar degrees of hypertension and renal function and may involve sex differences in renal NO metabolism.

Animals↗

The influence of sex difference in measurements with the Langham Ocular Blood Flow System.

PURPOSE: To assess sex difference and parameters possibly accounting for such a difference in healthy subjects evaluated by means of the Langham Ocular Blood Flow (OBF) System. METHODS: Pulse amplitude of intraocular pressure (IOP) and pulsatile ocular blood flow (POBF) as measured with the Langham OBF System were assessed in 86 healthy men and 69 healthy women. RESULTS: Compared to men, women showed higher POBF (mean +/- SD: 722.6 +/- 152.8 versus 647.8 +/- 164.9 microL/min; P =.0056) and pulse amplitude (mean +/- SD: 2.3 +/- 0.7 versus 2.0 +/- 0.6 mm Hg; P =.0043) values. Sex difference was still significant after correcting for age, refraction, blood pressure, IOP, and pulse rate. Pulse amplitude correlated negatively with pulse rate, and POBF correlated negatively with IOP. Women had higher readings in pulse amplitude and POBF, even after correcting for age, refraction, IOP, blood pressure, and pulse rate. CONCLUSIONS: While using the Langham OBF System, one needs to be aware of sex difference that is independent of other hemodynamic parameters. How the observed difference in POBF is related to ocular blood flow, and how it might influence the preponderance of various ocular diseases in men or women remains to be clarified.

Adolescent↗

Sex differences in schizophrenia: a commentary.

A critique is offered of Samuels' article suggesting that reported sex differences in concordance rates for schizophrenia are either methodological artifacts or a function of sociological processes. Evidence of sex differences in age of onset, clinical expression, concordance rates among primary relatives, and premorbid competence is cited. Finally, it is concluded that sex differences in schizophrenia offer important clues to the development of the disorder and should be considered in future theories of schizophrenia.

Age Factors↗

Effects of undernutrition and sex difference on skeletal muscle function in young rats.

The effects of undernutrition and sex difference on skeletal muscle contractile characteristics were studied in young albino rats. The skeletal muscle (gastrocnemius) of 8 week old pups with only one-third normal food intake (undernourished group = UN group; n = 18), as compared to free fed pups (control group = cont. group; n = 16), showed prolongation of contraction time (23.6 +/- 1.0 Vs 20.9 +/- 0.8 msec, Mean +/- SE, P < 0.05) and relaxation time (31.5 +/- 1.8 Vs 22.9 +/- 1.1 msec, P < 0.001) and retention of contraction force and endurance time. In 18 week old rats the effects of sex difference in females (n = 10), as compared to males (n = 10) were prolongation of contraction time in gastrocnemius (32.2 +/- 1.5 Vs 27.8 +/- 1.5 msec, P < 0.05), less force production in gastrocnemius (668.9 +/- 48.0 Vs 895.4 +/- 93.3 g, P < 0.05) and extensor digitorum longus (20.1 +/- 3.3 Vs 29.9 +/- 2.5 g, P < 0.05) and shorter endurance time (160.8 +/- 10.2 Vs 187.2 +/- 7.1 sec, P < 0.05) in soleus. Thus, it is concluded that early undernutrition has prolonged the contraction and relaxation times of the skeletal muscles and the effect of sex difference in the early adulthood was different in different skeletal muscles.

Animals↗