Sex differences and androgen-dependent regulation of aromatase (CYP19) mRNA expression in the developing and adult rat brain

Sex differences, androgen dependence and asymmetries of aromatase activity have been reported during ontogeny of the rat. It remains to be elucidated, however, whether the changes in aromatase activity are reflected by similar changes in specific mRNA levels. In addition, very little is known regarding mechanism(s) underlying such differential regulation of aromatase expression. To address these questions, we have employed the in situ hybridization (ISH) technique to examine specific mRNA levels in the brain of both male and female rats at selected stages of development. In prenatal stages of development, at gestational day (GD) 18 and 20, aromatase mRNA was detected in several hypothalamic and limbic brain regions. Semiquantitative analysis of aromatase mRNA did not reveal statistically significant sex differences in any of these regions (except in one experiment at GD20, when a sex difference was found in the medial preoptic nucleus). In contrast, clear sex differences were determined at postnatal day (PN) 2; male animals contained significantly more aromatase mRNA in the bed nucleus of the stria terminalis (BST) and the sexually dimorphic nucleus of the preoptic area (SDN) compared to female rats. Four days later in development, at PN6, sex differences of aromatase mRNA signals were observed in the BST, but were no longer detectable in the SDN. At PN15 and in adult animals, no sex differences could be determined. The effect of flutamide treatment (50 mg/kg/day) was investigated in GD20 fetuses as well as in adult rats. No statistically significant changes in aromatase mRNA expression were found in either case. In summary, our results suggest that differential regulation of aromatase mRNA expression during the critical period of sexual differentiation might, in part, account for the establishment of some of the many sexually dimorphic parameters of the rat brain. The role of androgens in the regulation of the sex-specific and developmental expression of aromatase mRNA in the rat brain remains to be clarified.     

Sex differences in the representation of visuospatial functions in the human brain.

Investigated sex differences in the representation of visuospatial functions in the human brain in 20 Ss with right hemisphere stroke and 40 stroke-free control Ss with the Complex Figure Test, Wechsler Adult Intelligence Scale—Revised (WAIS—R) Block Design, and Judgment of Line Orientation. Also, 3 models of sex differences in the representation of visuospatial functions in the human brain were evaluated. The stroke and control groups were composed of equal proportions of men and women. Results suggest that women may be disproportionately impaired in visuospatial functioning relative to men following right hemisphere stroke. It is proposed that visuospatial functions were bilaterally represented in the brains of men, allowing them to rely upon left hemisphere visuospatial systems following right hemisphere stroke, and that these functions were represented in the right hemisphere of women, resulting in their disproportionate impairment despite comparable lesions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex differences in morphology of the brain stem and cerebellum with normal ageing

The cerebral hemispheres become atrophic with age. The sex of the individual may affect this process. There are few studies of the effects of age and sex on the brain stem and cerebellum. We used MRI morphometry to study changes in these structures in 152 normal subjects over 40 years of age. In the linear measurements, men showed significant age-associated atrophy in the tegmentum and pretectum of the midbrain and the base of the pons. In women, only the pretectum of the midbrain showed significant ageing effects after the age of 50 years, and thereafter remained rather constant. Only men had significant age-associated reduction in area of the cerebellar vermis area after the age of 70 years. Both men and women showed supratentorial brain atrophy that progressed by decades. There were significant correlations between supratentorial brain atrophy and the diameter of the ventral midbrain, pretectum, and base of the pons in men, and between brain atrophy and the diameter of the fourth ventricle in women.     

New insights into the regulation and function of brain estrogen synthase (aromatase)

In the brain, conversion of androgens into estrogens by the enzyme aromatase (estrogen synthase) is a key mechanism by which testosterone regulates many physiological and behavioral processes, including the activation of male sexual behavior, brain sexual differentiation and negative feedback effects of steroid hormones on gonadotropin secretion. Studies on the distribution and regulation of brain aromatase have led to a new perspective on the control and function of this enzyme. A growing body of evidence indicates that the estrogen regulation of aromatase is, at least in part, trans-synaptic. Afferent catecholamine pathways appear to regulate aromatase activity in some brain areas and thereby provide a way for environmental cues to modulate this enzyme. The localization of aromatase in pre-synaptic boutons suggests possible roles for estrogens at the synapse.     

Identification of aromatase in the reptilian brain

The present study tests the hypothesis that brain aromatase is an "ancient" property of nervous tissue and may be identified in homologues of the limbic system in a non-mammalian vertebrate, the turtle Chrysemys picta. Tissue homogenates (180 mg wet weight/2 ml) were incubated with [7 alpha-3H]androstenedione and cofactors for 60 min at 37 C. Estrone (E1) was isolated and characterized by thin layer chromatography, methylation and recrystallization to constant specific activity. No estradiol-17 beta was detected. Aromatase was found only in the forebrain but was diffusely distributed throughout this major brain division. No other neural or non-neural tissues, including mid- and hindbrain structures, testis, and ovary, synthesized detectable quantities of E1 in our system. The strio-amygdaloid complex of both sexes synthesized more E1 per unit weight than the preoptic-hypothalamic area (POA-HTH) or other forebrain structures. It is possible that the conversion of androgen to estrogen has biological significance in this species since the reaction occurred throughout the physiological temperature range experienced during activity in nature and sex differences in brain aromatase activity during the breeding season were apparent. These experiments in Chrysemys demonstrate that the synthesis of estrogen from androgen by the brain is not limited to mammals, but also occurs at a more primitive level of phylogenetic development. Restriction of aromatase to forebrain structures of the turtle is consistent with the neuroanatomic distribution of enzyme activity in the limbic system of mammals. Estrogen yield from adult turtle brain incubates (3.2-22.6 pmol/g) is more like that reported for fetal (2.7-33 pmol/g) than for adult (0.1-1.9 pmol/g) mammals. We suggest that the in situ synthesis of estrogen by the central nervous system has its orgins early in vertebrate evolution and may be a primitive characteristic of brain-steroid interactions that regulate physiological and behavioral sex in vertebrates.     

Sex differences in brain regions activated by grammatical and reading tasks

Do the brains of men and women show similar patterns of functional organization for language, or are men more strongly lateralized? We used PET to measure cerebral blood flow (CBF) as men and women read real and nonce verbs, and produced past tense forms. While the overall patterns of reaction time, error, and brain activation were similar, there were also significant sex-related differences in CBF patterns. During the past tense generation tasks, men showed left-lateralized activation while women recruited bilateral perisylvian cortex, confirming differences in functional laterality. During all tasks, women showed higher activation in occipital and/or cerebellar regions, suggesting differences in basic reading strategies. We conclude that sex differences in functional cortical organization exist in the absence of significant behavioral differences.     

Sex differences in nitrite/nitrate levels and antioxidant defense in rat brain

This study assessed sex differences in stable metabolites of nitric oxide and major enzymes involved in antioxidant defense in various regions of rat brain. Nitrite/nitrate levels and activities of superoxide dismutase and catalase were determined in cortex, hippocampus, corpus striatum, midbrain and cerebellum of adult male and female Sprague-Dawley rats. Nitrite/nitrate levels were significantly higher in the cortex and the hippocampus of male than female rats, while catalase activity was higher in the cortex of females than in males. These sex differences may have significant effects on brain function in health and disease.     

Individual differences in cognitive abilities and brain organization: I. Sex and handedness differences in ability.

Analyzed data on cognitive abilities from 3 samples of normal Ss: (1) 195 undergraduates, (2) 215 18–30 yr old newly married couples, and (3) 122 pairs of monozygotic and dizygotic twins (aged 12–38 yrs). Findings reveal a common Sex by Handedness by Reasoning-Ability interaction: For Ss with above-median reasoning ability, spatial scores of left-handed males were reduced but those of left-handed females were raised, relative to their right-handed counterparts; the opposite pattern was found for Ss with below-median reasoning ability. The dependence of handedness effects on reasoning ability level appears to explain some of the inconsistent findings in the literature. Verbal fluency, perceptual speed, and visual memory also showed sex and handedness effects, which often interacted with level of reasoning ability or other cognitive variables. Results strongly suggest that sex and handedness differences in cognitive ability are partly neurological in origin. Variations in the effects of handedness across levels of reasoning ability (or other abilities) may indicate that different trade-offs among structural, and thus cognitive, characteristics will be found in different subsamples: There may be many kinds of normal brain organization. (French abstract) (98 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex differences in brain and personality correlates of the ability to identify popular word associations.

The ability of men to identify popular word associations had earlier been shown to be affected by left-sided thalamic surgery for movement disorders; now, over a year later, the impairment has been observed with operations on both sides. In addition, upon testing at approximately the same time interval, men who had undergone temporal lobe surgery for epilepsy have also shown the impairment. In contrast, women have improved after the operations. The Word Association Test (WAT) requires a subject to identify popular word associations to 54 words. In a large group of unoperated subjects, the errors on the WAT were greater for men than for women, although the men scored higher on the Wechsler-Bellevue Intelligence Scale (WB). WAT scores were found to correlate with scores on the WB and the Minnesota Multiphasic Personality Inventory (MMPI), and the WAT scores of the men tended to show a higher correlation with these measures than did those of the women. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex differences in influenceability.

Examines the hypothesis that women are more influenceable than men in a variety of situations. For persuasion research and for conformity studies not involving group pressure, there is scant empirical support for a sex difference, and for group pressure conformity research, there is support among a substantial minority of studies. Also explored is the possibility that various sex differences in social influence studies are a product of contextual features of experimental settings. This is suggested by the fact that findings reporting greater influenceability among females were more prevalent in studies published prior to 1970 than in those published in the 1970s. Finally, sex differences in various psychological processes that may mediate persuasion and conformity are evaluated as possible explanations for those influenceability sex differences that appear to be genuine. It is suggested that a propensity to yield inherent in the female sex role appears to account for some aspects of influenceability findings, but a 2nd explanation, a tendency for women more than men to be oriented to interpersonal goals in group settings, is also plausible. (7? p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex differences in persistent fatigue

This study examines factors differentiating women and men who suffer from fatigue. It is based on diaries kept by Dutch citizens over a 21-day period between 1987-88. The majority of those with persistent fatigue complaints (PFs) were male, middle-aged, lower-educated and unemployed, and they had more psychological and psycho-social problems than the incidental fatigue sufferers (IFs). Factors differentiating the PFs from the IFs are not the same for both sexes. Moreover, on a number of socio-demographic variables PF men and women differed less from each other than IF men and women. Future research should focus on the gender-specificity of the factors that lead to the development of persistent fatigue.     

Sex differences in occupational performance

Nineteen patients with cystic fibrosis were seen in the I Department of Tuberculosis and Lung Diseases during 3.5 years. There were 12 (63%) female, and 7 male, aged from 16 to 35 years (mean 23.2). Most patients were diagnosed in childhood, but 4 were diagnosed in their early adulthood. The diagnosis was confirmed by positive chloride sweat test in all cases. Molecular DNA analyses were performed in 16 cases. In 9 (56%) cases two mutations in the CFTR gene were identified. In 5 cases one mutation was identified. All patients had bronchiectases confirmed by CT. Spirometry showed lung function impairment with predominantly obstructive pattern. Mean VC was 2.57l, mean FEVI was 1.66l. In 7 (37%) cases FEVI was lower then 30% of predictive value. Hypoxemia was found in 11 (58%) cases and hypercapnia in 3 (16%) cases. Sputum cultures were positive for mucoid P. aeruginosa in 12 (63%) cases, for Staph. aureus in 16 (84%) cases. Persistent colonisation with nontuberculous mycobacteria was found in 2 (10.5%) cases. Aspergillus fumigatus was identified in sputum cultures in 2 subjects who had also positive precipitation test. Diabetes mellitus was diagnosed in 2 cases. Meconium ileus equivalent was seen in 1 case. Pneumothorax was seen in 1 case. One patient died in the endstage of the illness.     

Sex differences in the nervous system of reptiles

1. The study of sex differences in the brain and behavior of reptiles presents an excellent opportunity both to discern general principles of sexual differentiation in the nervous system and to explore the evolutionary history of this process in amniote vertebrates. 2. Findings in several reptiles suggest that some sex differences found in mammals and birds are conserved while others are not. Conserved features include areas in the limbic forebrain involved in the regulation of social and sexual behaviors. As in mammals and birds, it is rare to find differences in the distribution of sex steroid concentrating neurons in reptiles but common to find differences in the distribution of the various steroid hormone receptors and in their regulation. 3. This research has revealed that differences in social and sexual behavior are reflected better by the activity, not by the size, of hormone-sensitive limbic areas. 4. Finally, species differences in plasma levels of sex hormones are paralleled by differences in behavioral sensitivity to these hormones as well as by differences in the regulation of genes coding for steroid hormone receptors.     

Sex differences in the recall of affective experiences

Three studies tested hypotheses for sex differences in the recall of life events: differences in (a) affect intensity at encoding, (b) affect intensity at retrieval, (c) rehearsal, (d) detail of encoding, and (e) artifacts such as motivation or verbal ability. In Study 1 (N = 419), women recalled more positive (p < .01) and more negative (p < .05) life events than men. Differences in retrieval mood were not found. Study 2 (N = 55) replicated the recall differences and showed that neither rehearsal nor artifacts were responsible. Sex differences in recalling neutral everyday events also were obtained (p < .05), suggesting that affect intensity was not responsible. In Study 3 (N = 132), affective reactions to events were unrelated to recall, but sex differences in the detail of encoding (p < .001) were related to recall (p < .05). Sex differences in autobiographical memory are reliable and may be due to differences in the detail of encoding.     

Sex differences in the allocation of pay.

Examined the possibility that relative to males, females perceive less of a connection between their work and monetary rewards. In Study 1, 66 females and 60 males (respondents to an advertisement in a student newspaper) determined either their own pay or the pay of another person. Results support the hypothesis in that females paid themselves less than did males and less than other people (males or females) paid females. Results also suggest that Ss were more generous when they paid females. In Study 2, sex differences in self-pay were examined in 80 1st-, 4th-, 7th-, and 10th-grade Ss. Results replicate those of Study 1, in that at every grade level, females paid themselves less than did males. In addition, the extent to which females allocated pay the way their male counterparts did was highly related to the masculinity of their career goals. (18 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex differences in dehydroepiandrosterone-induced hepatocarcinogenesis in the rat

The direct quantification of antibiotics in agar allows one to study the quality of the agar matrix, the kinetics of diffusion and the bacteria-antibiotic interaction. Mueller-Hinton agar (MHA) plates from three manufacturers were tested using HPLC and the disc diffusion test of ceftazidime (CAZ). Notable differences in the chromatographic profiles of MHA plate extracts from OXOID, DID and Becton Dickinson (BD) were shown, with a higher CAZ concentration after 24 h a 6 mm in BD P. aeruginosa inoculated plates (5.1 +/- 1.7 micrograms/ml, n = 6) vs. OXOID and DID (1.6 +/- 0.3 micrograms/ml, n = 12). BD plates gave also a different inhibition zone diameter (26 +/- 0.5 mm, n = 3) with respect to DID and OXOID (29 +/- 0.5 mm, n = 3).     

Sex differences in prefrontal cortical brain activity during fMRI of auditory verbal working memory.

Functional imaging studies of sex effects in working memory (WMEM) are few, despite significant normal sex differences in brain regions implicated in WMEM. This functional MRI (fMRI) study tested for sex effects in an auditory verbal WMEM task in prefrontal, parietal, cingulate, and insula regions. Fourteen healthy, right-handed community subjects were comparable between the sexes, including on WMEM performance. Per statistical parametric mapping, women exhibited greater signal intensity changes in middle, inferior, and orbital prefrontal cortices than men (corrected for multiple comparisons). A test of mixed-sex groups, comparable on performance, showed no significant differences in the hypothesized regions, providing evidence for discriminant validity for significant sex differences. The findings suggest that combining men and women in fMRI studies of cognition may obscure or bias results. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex differences in corticosteroids in man

The serum concentrations of progesterone (P), 17-OH-progesterone (17-OHP), 11-deoxycorticosterone (DOC), corticosterone (B), 11-deoxycortisol (S), 18-OH-11-deoxycorticosterone (18-OH-DOC), aldosterone (Aldo) and cortisol (F) were measured in 18 normal men (M), 14 normal women in the folicular phase (FF) and 14 normal women in the luteal phase (FL) of menstrual cycle from blood samples obtained between 0800 and 0900 h. Steroids were estimated by a sensitive and specific radioimmunoassay allowing the simultaneous determination of all steroids studied from one 3 ml serum sample. The mean steroid concentrations (ng/1dl) in FF were found to be as follows: P, 20.3; 17-OHP, 58; DOC, 3.8; B, 241; S, 20.7; 18-OH-DOC, 12.3; Aldo, 8.8; F, 9860. Apart from P, steroid concentrations in FF were significantly lower than in M. Serum 17-OHP, DOC, B and Aldo in FF were significantly lower than in FL. With the exception of P, there were no significant differences of mean steroid concentrations between M and FL.     

Sex differences and IQ

Ciliary ganglion (CG) neurons, like other neuronal populations, become dependent on their targets for survival during development. We have previously purified and cloned a secreted ciliary neurotrophic factor that was called growth-promoting activity (GPA). We report here the expression and purification of a highly active form of recombinant GPA, the preparation of GPA-specific polyclonal and monoclonal antibodies, and the use of these antibodies to investigate the cellular location and timing of GPA expression in tissues innervated by CG neurons. Virtually all of the trophic activity in extracts of embryonic eyes could be depleted by GPA-specific antibodies. GPA-like immunoreactivity was found in both targets of the CG: the arterial vasculature of the choroid layer and the ciliary body of the eye. In the choroid layer, GPA was localized to smooth muscle cells surrounding the choroid arteries. Staining in the choroid layer was first detectable at embryonic day (E) 10, or about 2 days after cell death has begun in the ganglion, then increased in intensity through E19. Quantification of trophic activity from whole eye extracts at various ages showed a small increase in activity observed between E9 and E12 and at least a 10-fold increase between E12 and E18. The presence of GPA protein in target cells of CG neurons during the specific developmental period when these neurons undergo cell death is consistent with its proposed function as a target-derived ciliary neurotrophic factor.     

Sex differences in problem solving.

Used a 20-item set of problems (similar to those used by E. Sweeney [1953]) in 9 experiments with 558 male and 578 female undergraduates to determine which sex was superior in problem solving, the role of previous experience, whether sex differences extended throughout the domain of problem-solving tasks, whether they extended to other word problems, the role of spatial ability and verbal ability, the role of mathematics aptitude, and the relative importance of aptitude and social learning variables. Results show that the male advantage, averaging 35% across experiments, persisted at the same level as in experiments conducted in the 1950's. Sex differences extended to other word problems. The male advantage was related to similar advantages in spatial and mathematical ability. Aptitude variables dominated attitude and mathematics experience variables in accounting for the sex difference. (48 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)