Corpus callosum: effects of neonatal hormones on sexual dimorphism in the rat

The rat's corpus callosum is sexually dimorphic, with the male's being larger. In addition, giving rats extra stimulation in infancy via handling increases callosal area in males, but not in females. To determine if this dimorphism is testosterone-dependent, male pups were castrated on Day 1 of life while females received an injection of testosterone propionate (TP) on Day 4. Control males had sham surgery and control females received an injection of sesame oil. All animals were handled daily from birth until weaning. Animals were sacrificed at 110 days and a mid-sagittal section of the callosum was obtained. From this section measures of callosal area, perimeter, length, and 99 widths were derived. We verified our previous finding that the male callosum is larger than that of the female. Neonatal TP treatment masculinized the callosa of the females, but castration did not affect the males. TP treatment affected the width dimension of the callosum but not callosal length or brain weight. In a related study the synthetic estrogen DES did not increase callosal size for castrated males or for intact females, while the estrogen blocker, tamoxifen, had a defeminizing effect on females' callosa. These findings suggest that there is an estrogen-dependent active process of feminization of cortical tissue in the female brain.     

Cerebral sex dimorphism and sexual orientation

The neurobiology of sexual orientation is frequently discussed in terms of cerebral sex dimorphism (defining both functional and structural sex differences). Yet, the information about possible cerebral differences between sex‐matched homo and heterosexual persons is limited, particularly among women. In this multimodal MRI study, we addressed these issues by investigating possible cerebral differences between homo and heterosexual persons, and by asking whether there is any sex difference in this aspect. Measurements of cortical thickness (Cth), subcortical volumes, and functional and structural resting‐state connections among 40 heterosexual males (HeM) and 40 heterosexual females (HeF) were compared with those of 30 homosexual males (HoM) and 30 homosexual females (HoF). Congruent with previous reports, sex differences were detected in heterosexual controls with regard to fractional anisotropy (FA), Cth, and several subcortical volumes. Homosexual groups did not display any sex differences in FA values. Furthermore, their functional connectivity was significantly less pronounced in the mesial prefrontal and precuneus regions. In these two particular regions, HoM also displayed thicker cerebral cortex than other groups, whereas HoF did not differ from HeF. In addition, in HoM the parietal Cth showed “sex‐reversed” values, not observed in HoF. Homosexual orientation seems associated with a less pronounced sexual differentiation of white matter tracts and a less pronounced functional connectivity of the self‐referential networks compared to heterosexual orientation. Analyses of Cth suggest that male and female homosexuality are not simple analogues of each other and that differences from heterosexual controls are more pronounced in HoM.     

Reversal of hippocampal sexual dimorphism by gonadal steroid manipulation

Hippocampal slices display a sexually dimorphic pattern of physiological neuromodulation to gonadal steroid administration. To determine if this is the result of organizational or activational hormone action, plasma steroid levels of adult male rats were manipulated. The results support an activational mechanism since steroid levels can be manipulated to abolish, reverse, or maintain the functional dimorphism. The results suggest a role for gonadal steroid action in rapid neuromodulation of brain function.     

Neurobehavioral hemispheric preferences: a case of sexual dimorphism

Ninety subjects (47 females and 43 males) with age ranging from 17 to 25 completed a neurobehavioral inventory of hemispheric preference. The inventory (Wagner & Wells, 1985) consists of 12 items, each of which has 4 statements that relate to four different functions of the two hemispheres namely: (a) Left-logical (b) Left-verbal (c) Right-manipulative/spatial and (d) Right-creative. The results indicated an overall preference for verbal-logical tasks. This preference pattern was more pronounced in males than in the female subjects. Also, the female subjects exhibited greater preference for creative tasks (activities), whereas the males showed preference for verbal tasks. These results suggests that proficiency and preference may not necessarily follow the similar pattern.     

Modulation of oxytocin secretion by ascending noradrenergic pathways: sexual dimorphism in rats

We have investigated the role of ascending noradrenergic pathways in the control of oxytocin (OT) and arginine-vasopressin (AVP) secretion during acute immobilization stress in male and female rats. 6-Hydroxydopamine-induced lesions of the ventral noradrenergic bundle (VNAB) resulted in a selective depletion of hypothalamic noradrenaline content. In sham-lesioned rats plasma levels of OT were raised following stress, the response being significantly greater in female compared with male animals. VNAB lesions were not associated with altered responses in female rats, whereas lesioned males exhibited markedly elevated OT stress responses. AVP secretion was not modulated in VNAB-lesioned rats of either sex. The results provide functional evidence of a sexually dimorphic inhibitory role of the VNAB in the control of OT secretion.     

Oxytocin-induced inhibition of feeding and drinking: no sexual dimorphism in rats.

The effect of oxytocin on feeding and drinking behaviours was compared in male and female rats. Dose-dependent feeding and drinking inhibition was observed in either sex to about the same degree, both following intracerebroventricular or intraperitoneal administration. The results were obtained whether in animals with free access to food and water or in schedule-fed animals fasting for 21h and in two different models of thirst (water deprivation for 16h, s.c. administration of hypertonic saline). These data show that there is no sexual dimorphism in oxytocin-induced inhibition of feeding and drinking.     

Hypothalamic resetting at puberty and the sexual dimorphism of migraine

It is well known that migraine is far more represented in females than in males. However, this gender-related difference is present only during reproductive life since in prepubertal children, migraine prevalence figures are independent of sex. Thus, transition to puberty accounts for changes which render females more susceptible to migraine attacks. In females, the main driver of the hormonal events allowing sexual maturation is the pulsatile secretion of hypothalamic LHRH modulated by opioid activity. Clinical reports suggest that migraine attacks could be prevented by the abolition of this neurohormonal secretion. On the other hand, several clinical and experimental observations have focused on neuroendocrine systems (opiatergic, serotonergic, adrenergic) as participating in the constitution of the so-called "migraine trait", the biological predisposition in patients that would explain their sensitivity to migraine triggers. Such neuroendocrine secretions are mainly dependent upon hypothalamic activity where a sexual dimorphic nucleus has been discovered in the preoptic area. We suggest that the sexual dimorphism of migraine should be sought in hypothalamic networks related to LHRH secretion.     

Alcoholism and sexual dimorphism in the middle longitudinal fascicle: a pilot study

Alcoholism can lead to a complex mixture of cognitive and emotional deficits associated with abnormalities in fronto-cortico-striatal-limbic brain circuitries. Given the broad variety of neurobehavioral symptoms, one would also expect alterations of postrolandic neocortical systems. Thus, we used diffusion tensor imaging (DTI) to study the integrity of the middle longitudinal fascicle (MdLF), a major postrolandic association white matter tract that extends from the superior temporal gyrus to the parietal and occipital lobes, in individuals with a history of chronic alcohol abuse. DTI data were acquired on a 3 Tesla scanner in 30 abstinent alcoholics (AL; 9 men) and 25 nonalcoholic controls (NC; 8 men). The MdLF was determined using DTI-based tractography. Volume of the tract, fractional anisotropy (FA), radial (RD), and axial (AD) diffusivity, were compared between AL and NC, with sex and hemispheric laterality as independent variables. The association of DTI measures with neuropsychological performance was evaluated. Men showed bilateral reduction of MdLF volume and abnormal diffusion measurements of the left MdLF. Analyses also indicated that the left MdLF diffusion measurements in AL men were negatively associated with Verbal IQ and verbal fluency test scores. Abstinent alcoholic men display macrostructural abnormalities in the MdLF bilaterally, indicating an overall white matter deficit. Additionally, microstructural deficits of the left MdLF suggest more specific alterations associated with verbal skills in men.     

Re-evaluation of sexual dimorphism in human corpus callosum.

To study the sexual dimorphism of human corpus cauosum (CC), we analyzed the midsaggital magnetic resonance imaging (MRI) morphometry in 67 adults aged (mean+/-s.d.) 36.82+/-9.35 years. Four specific angles of the CC were determined. All four angles in 34 females and 33 age-matched males showed a significant difference between females and males. These morphometric findings confirm a gender difference in the orientation of corpus callosum.     

Antikindling effects of locus coeruleus stimulation: mediation by ascending noradrenergic projections

Electrical stimulation of the noradrenergic locus coeruleus (LC) delays the generalization of partial seizures during amygdaloid kindling by increasing the time spent in the earliest stages of seizure development. To determine whether noradrenergic axons projecting to the midbrain and forebrain are involved in this antikindling effect, we examined the effects of lesions of the dorsal noradrenergic bundle, induced by intracerebral infusions of 6-hydroxydopamine (6-OHDA), on kindling and the antikindling action of stimulation of the LC. Stimulation of the LC during amygdaloid kindling increased the number of afterdischarges (ADs) spent in the early stages of partial seizure and decreased the number of ADs spent in later stages of generalized seizure, as has been described previously. LC-stimulated rats also displayed longer durations of AD during early stages of kindling. The antikindling effect of LC stimulation was blocked by lesions of the dorsal bundle, whereas the facilitatory effects of LC stimulation on generalization and on the duration of AD were unaffected by the lesions. These results suggest that the antikindling action of LC stimulation is mediated by the ascending projections of noradrenergic neurons, presumably through enhanced release of noradrenaline. On the other hand, the facilitatory effects of LC stimulation on the development of later stages of seizure and on the duration of AD appear to be independent of the ascending dorsal bundle.     

Neurophysiological correlates for the perception of facial sexual dimorphism

Neural correlates for the processing of face identity, expression, gaze direction and attractiveness are well described, but neurophysiological correlates for the perception of face gender are less understood. Here, we used morphing techniques to produce synthetic faces with graded perceivable gender and independent component analysis (ICA) of multifocal EEG to unravel neural signals correlated to processing and perception of face gender. We investigate possible neural correlates of face perception using scalp event-related potentials (ERPs) and dipole source analysis in a group of health observers. We isolated one signal source localised to the right parieto-temporal region with a latency of about 170 ms, whose latency correlates with perceived facial masculinity. In conclusion, our data prove that the right parieto-temporal regions play a fundamental role in face gender masculinity processing and perception in humans.     

Forms and measures of adult and developing human corpus callosum: Is there sexual dimorphism?

The sexual dimorphism of the human corpus callosum (CC) is currently controversial, possibly because of difficulties in morphometric analysis. We have reinvestigated the issue by using morphometric techniques specially designed to yield objective measurements of CC size and shape. The development of the CC was studied with similar techniques in order to investigate whether its final shape and size might be influenced by axonal elimination, as could be expected from previous animal studies. We have measured the CCs of 32 men and 26 women; 27 male and 19 female CCs were from brain tissue, the others were from magnetic resonance imaging graphs. Women tended to have 1) a smaller cross-sectional callosal area (CCA); 2) a larger fraction of CCA in the posterior fifth of the CC; 3) more slender CCs; and 4) more bulbous splenia. These differences could not be detected by simple inspection but were demonstrated by measurement and statistical analysis. However, CCA was correlated with the other sexually dimorphic parameters, and the sex-related differences in the latter became nonsignificant when variations in CCA were factored out or when male and female populations with similar CCA were compared. In addition, we analyzed CCs of 16 male and 16 female fetuses and of 13 male and 15 female infants and children. This sample ranged in age between 20 weeks of gestation and 14 years but covered in detail the period up to 14 months after birth. CCA increased throughout the latter period but decreased slightly between about 33 weeks of gestation and the beginning of the second postnatal mouth. This decrease coincided with thinning of the CC and a marked increase in bulbosity of the splenium. No sexual dimorphism could be demonstrated until the beginning of the postnatal period. In the age group between birth (at term) and the 14th month, CCA was, as in the adult, larger in males. Unlike in the adults, the CC was longer in males and the bulbosity index was the same in the two sexes. Axonal elimination may play a role in the perinatal pause in CCA growth and in the concomitant changes in callosal shape.     

Role of adrenal medulla in development of sexual dimorphism in inflammation

Many inflammatory diseases show a female predilection in adults, but not prepubertally. Because sex differences in the inflammatory response in the adult rat are mediated, in part, by sexual dimorphism in adrenal medullary function, we investigated the contribution of the adrenal medulla to the ontogeny of sexual dimorphism in inflammation. Whilst there was no sex difference in the magnitude of the plasma extravasation (PE) induced by the potent inflammatory mediator bradykinin (BK) in prepubertal rats, in adult rats BK-induced PE was markedly greater in males. Also, adult male rats, gonadectomized prior to puberty, had a lower magnitude of BK-induced PE than did adult male controls, whilst adult females gonadectomized prepubertally had higher BK-induced PE than did controls. In rats gonadectomized after puberty, the magnitude of BK-induced PE in adult males was not affected, whilst in females it resulted in significantly higher BK-induced PE, similar to the effect of prepubertal gonadectomy. When tested prepubertally, adrenal denervation increased the magnitude of BK-induced PE in females, but not in males. In contrast, in both males and females tested as adults, but castrated prepubertally, and in gonad-intact adult females, adrenal denervation significantly increased the magnitude of BK-induced PE. Adrenal denervation in prepubertal females given adult levels of 17beta-oestradiol produced a marked enhancement in the denervation-induced increase in magnitude of BK-induced PE compared to females not exposed prematurely to sex hormones. These studies suggest that an adrenal medulla-dependent inhibition of BK-induced PE is present in female but not male rats, and is enhanced by oestrogen but suppressed by testosterone.     

The controversy about a sexual dimorphism of the human corpus callosum

A sexual dimorphism of the splenium corporis callosi in man was reported in 1982. The authors described the posterior part of the female corpus callosum to be larger and more bulbous than its male counterpart. From the lateralization research, it has previously been stated that the female brain is less well lateralized for visuospatial functions than the male. The authors postulated that a larger splenium implies a larger number of fibers and that the number of interhemispheric fibers correlates inversely with lateralization of function. However, their sample was very small and not adequately matched for sex. Therefore, we reinvestigated this question. A standardized computer assisted program will be presented. With this program the "classical" parameters have been evaluated and the "rotatory diameter measurement" was performed. No differences between the sexes were seen either for the splenium corporis callosi or for the other parts of the corpus callosum.     

E-series prostaglandins and arginine vasopressin in the modulation of male sexual behavior

Studies carried out recently in the author's laboratory have suggested that fever accompanies copulation in the male rat. Given the action of prostaglandin-E (PGE) in the genesis of fever and given the integrative role of the medial preoptic area (MPOA) in the expression of both fever and male sexual behavior, two hypotheses were advanced concerning male copulation. The first concerns PGE in facilitating transmission in MPOA pathways mediating mounting, intromission and ejaculation. The second concerns arginine vasopressin, a presumed "natural antagonist" of PGE, in inhibiting such transmission and eventually making the male refractory to the receptive female. Several experiments were suggested for testing each hypothesis.     

A comparison of hypothalami of rats and mice: lack of gross sexual dimorphism in the mouse

Anterior hypothalami from 10 male and 10 female CBA/j type mice were sectioned serially and examined histologically for possible sexual dimorphisms in appearance and size of neuronal aggregations. Measurements of volumes of suprachiasmatic nuclei and an adjacent cell aggregation, designated as the medial portion of the anterior hypothalamic nucleus (AHm) and similar in appearance and position to the sexually dimorphic nucleus of the rat, were made. In contrast to known sexual dimorphism present in the rat, no sex differences in volumes of mouse hypothalamic structures were found. This lack of gross sexual dimorphism in the mouse could be explained by (a) insensitivity of dividing and developing AHm neurons to androgens, or by (b) a possible influence of androgens upon overall AHm morphology in both sexes, due to transfer of androgens from males to females in utero.     

Midsagittal structural differences and sexual dimorphism of the corpus callosum in obsessive-compulsive disorder

Neurobiological abnormalities in various brain regions, including the orbitofrontal cortex, basal ganglia, and thalamus, have been found in patients with obsessive-compulsive disorder (OCD), and impairment in white matter connectivity in these regions has recently been suggested. To investigate structural connectivity in OCD, we used the midsagittal area and thickness to assess the morphology of the corpus callosum (CC), the largest connecting fiber tract in the human brain. Midsagittal magnetic resonance images of the CC were acquired from 69 adult patients with OCD and 69 matched normal controls. We calculated and compared the total area and the areas of five subregions of the CC as well as the distances between 200 equidistant points on the top and bottom of lines on the surface of the CC in the two groups. The absolute total area of the CC was significantly larger in OCD patients than in controls when brain size, age, gender, and IQ were controlled. Significant enlargements in CC1, CC2, and CC5 were seen in OCD patients before correction for multiple comparisons. The thickness of the caudal part of the splenium was greater in OCD patients than in controls. The analysis according to gender showed that only male OCD patients differed from male controls with respect to the area of the CC. These findings reflect structural abnormalities in the CC, and especially in the splenium, in adult patients with OCD. Abnormal interhemispheric connectivity, including the parietotemporal and occipital areas, may affect the pathophysiology of OCD. Sexual dimorphism in the CC of OCD patients should be considered.