The effect of gonadectomy on interhemispheric asymmetry in rats

The influence was studied of the gonadectomy in the newborn and mature male and female rats on functional interhemispheric asymmetry of the reaction of avoidance of pain scream of another rat ("emotional resonance"), and motor and investigatory activity in the open field. Consecutive inactivation of the hemispheres was realized by K+ spreading depression. It has been shown that neonatally gonadectomized rats have no interhemispheric asymmetry of the studied reactions. In male rats gonadectomized in mature state, interhemispheric asymmetry of "the emotional resonance" reaction is not significant and in the motor and investigatory activity in the open field, in contrast to intact animals, the right hemisphere is dominant and not the left one. Ovariectomy of mature female rats led to the increase of the dominance of the left hemisphere in the control of "the emotional resonance" and change of the right hemispheric dominance in the control of the motor and investigatory activity in the open field for the left hemispheric one. Gonadectomy of male and female mature rats had an opposite effect on the functioning of the right hemisphere: facilitating in male rats and inhibitory in female ones.     

Differential effects of testosterone metabolites in the neonatal period on open-field behavior and lordosis in the rat

Two experiments were done to compare the effects of neonatal exposure to testosterone and its major metabolites, dihydrotestosterone (DHT) and estradiol (E₂), on the development of sex differences in open-field behavior in the rat. In Experiment 1 female rats administered either testosterone propionate (TP), DHT, or estradiol benzoate (EB) were found as adults to have low activity scores, more typical of adult males, when compared to the high scores of oil-treated females. In Experiment 2 the adult open-field behavior of female rats treated neonatally with testosterone or the metabolites was compared to that of male rats treated from Day 1 to 10 of life with the aromatizing enzyme inhibitor, androst-1,4,6-triene-3,17-dione (ATD). These same animals were later tested for lordotic behavior after gonadectomy and priming with EB and progesterone. All male animals and female animals exposed neonatally to testosterone or to either of the metabolites had suppressed open-field activity scores compared to oil-treated females. However, the lordotic behavior of females exposed to DHT and of males exposed to ATD was not defeminized and was comparable to that of oil-treated females. These observations were discussed in terms of a role for the androgenic actions of testosterone in establishing sex differences in nonreproductive behavior in the rat.     

Estradiol is responsible for reduced renal prostaglandin dehydrogenase activity in female rats

The contribution of sex steroids to sex-related differences in renal prostaglandin dehydrogenase activity and urinary prostaglandin excretion was examined in 7-8-week-old male and female rats subjected to sham-operation or gonadectomy at 3 weeks of age. Rats were injected subcutaneously twice over a 6-day interval with vehicle (peanut oil, 0.5 mg/kg) or with depot forms of testosterone (10 mg/kg), estradiol (0.1 mg/kg), progesterone (5 mg/kg), or with estradiol and progesterone combined (0.1 and 5 mg/kg). After the second injection, 24-h urine samples were collected for prostaglandin measurement by radioimmunoassay; the rats were killed, and renal and pulmonary prostaglandin dehydrogenase activities were determined by radiochemical assay. Renal prostaglandin dehydrogenase activity was 10-times higher in intact male rats than in intact females. Gonadectomy increased renal prostaglandin dehydrogenase activity 4-fold in females, but had no effect in males; estradiol, alone or combined with progesterone, markedly suppressed renal prostaglandin dehydrogenase activity in both sexes, while testosterone or progesterone alone had no effect. Pulmonary prostaglandin dehydrogenase did not differ between the sexes and was unaffected by gonadectomy or sex-steroid treatment. Intact female sham-operated rats excreted 70-100% more prostaglandin E2, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha in urine than did males; gonadectomy abolished the difference in urinary prostaglandin E2 excretion. Estradiol decreased urinary prostaglandin E2 in females but not in males; treatment with other sex steroids did not alter urinary prostaglandin excretion.     

Interhemispheric asymmetry of positive emotional reactions in rats

Interhemispheric asymmetry of positive emotional reactions was studied in rats: satisfaction of drinking need and self-stimulation. Successive inactivation of the hemispheres was carried out by potassium spreading depression. Switching off of the right as well as the left hemispheres symmetrically influenced the whole quantity of the water, drunk by the rats to a full thirst satisfaction, i. e. the magnitude of need. However, at different stages of drinking need satisfaction an interhemispheric asymmetry was observed: under a strong drinking motivation the right hemisphere dominated, under a weak motivation--the left one. Switching off of the right hemisphere lowered the frequency of self-stimulation of the lateral hypothalamus and switching off the left one heightened it, testifying to the dominance of the right hemisphere in the reaction of self-stimulation. This reaction was also characterized by asymmetry of the lateral hypothalamus nuclei; reactivity to hemispheres inactivation (decreasing or increasing of self-stimulation frequency) of the right nucleus was more expressed than that of the left one.     

Interhemispheric asymmetry of "emotional resonance" in the rat

Hemispheric asymmetry of "emotional resonance" elaborated by the method of P.V. Simonov was studied in Wistar rats. Inactivation of hemispheres was carried out by means of spreading depression. When using as "victims" and "recipients" the animals of the same sex, lateralization of emotional resonance was found to depend upon the velocity of reaction elaboration. In rats rapidly elaborating avoidance reaction the right hemisphere dominated during its performance and so did the left one in animals learning after additional training. When using the animals of different sex as "victims" and "recipients", the right hemisphere dominated in "emotional resonance" performance. Hemispheric asymmetry of "emotional" resonance was more expressed in males than in females.     

Effects of testosterone and estrogen on hepatic levels of cytochromes P450 2C7 and P450 2C11 in the rat.

The effects of exogenous hormone treatment on the expression of cytochromes P450 2C7 and P450 2C11 were studied in neonatally gonadectomized and sham-operated male and female rats. Hepatic levels of cytochrome P450 2C7 were found to be two- to threefold higher in intact adult female versus male rats. Neonatal gonadectomy resulted in a reversal of the relative cytochrome P450 2C7 levels in male and female animals at maturity. Expression of this isozyme was restored in ovariectomized females by estradiol treatment. Furthermore, neonatal and/or pubertal administration of estradiol to intact male rats induced cytochrome P450 2C7 to adult female levels. On the other hand, administration of testosterone at all times examined had no effect in intact female rats, but decreased cytochrome P450 2C7 to normal levels in neonatally castrated males treated during adulthood. Neonatal testosterone treatment also increased hepatic cytochrome P450 2C7 content in both ovariectomized females and intact males. These results indicate that estrogen is required for full expression of cytochrome P450 2C7 while the effect of testosterone is ambiguous. In comparison, neonatal gonadectomy of male rats abolished the adult expression of cytochrome P450 2C11. Normal levels were restored only by treatment with testosterone during adulthood. Neonatal testosterone treatment did not induce cytochrome P450 2C11 levels in gonadectomized rats of either sex. In contrast, neonatal estrogen treatment suppressed cytochrome P450 2C11 expression in intact adult male rats to the same extent as neonatal castration. These results indicate that androgen exposure during the adult, and not the neonatal, phase is essential for full expression of cytochrome P450 2C11.     

Sexual differences in the interhemispheric asymmetry of the transcallosal responses of the associative areas in the cat neocortex

Sex differences of hemisphere asymmetry of homo- and heterotopic transcallosal responses in association cortex of 48 cats (24 male and 24 female) immobilized by tubocurarine have been studied by means of topographic EPs recordings in both hemispheres. In males left hemisphere dominates by the amplitude of homotopic and positive wave of heterotopic EPs and right hemisphere dominates by the amplitude of negative wave of heterotopic sensorimotor cortex EPs. The individual asymmetry of EPs has been observed in sensomotor cortex of females and in parietal cortex of animals of both sex. The interhemispheric asymmetry is expressed distinctly in females than in males. It is concluded that sex dimorphism is present in functional organization of associative system of (callosal and intracortical) connections in cat's neocortex projection and association areas which means its more expressed hemisphere lateralization in males with more expressed interhemispheric asymmetry of functional transcallosal connections in females.     

Testosterone and estradiol produce different effects on cognitive performance in male rats

The effects of castration and hormone treatment on cognitive performance were evaluated in male rats. Castrated animals received either testosterone or estradiol and were compared with gonadally intact animals and with castrated controls. Results revealed a dissociation between the effects of testosterone and estradiol on cognitive performance in male rats. Specifically, estradiol enhanced acquisition of a delayed matching-to-position spatial task, similar to previously published observations in females. In contrast, neither castration nor testosterone treatment had any significant effect on acquisition of the delayed matching-to-position task, but did appear to affect delay-dependent working memory. None of the treatments had any significant effect on acquisition of a configural association negative patterning task, suggesting that effects on the delayed matching-to-position task were not due to effects on motivational factors. These data demonstrate that, as in females, gonadal hormones influence cognitive performance in males and suggest that estradiol and testosterone affect distinct cognitive domains.     

Gender dependent effects of testosterone and 17β-estradiol on bone growth and modelling in young mice

This study examined the effects of estrogen (17β-estradiol) and testosterone on the growth of long bones in male and female mice, with and without gonadectomy. Weight and nose-to-tail length were determined at 3 weeks of age at time of gonadectomy, 7 days later at the onset of hormone therapy, and throughout the treatment period. Gonadectomized mice exhibited an initial weight gain during the pretreatment period but length was unaffected. Hormone treatment altered weight gain in surgical and intact animals in a gender- and hormone-dependent manner. Estradiol enhanced weight gain in intact mice, but inhibited weight gain in ovariectomized mice. Lower doses of estradiol increased weight gain in orchiectomized mice at early time points. Testosterone increased weight in intact females and males, but not in gonadectomized mice. Estradiol increased nose-to-tail length in intact females at early time points, but inhibited length in ovariectomized females at later times, and it decreased length in intact males. Testosterone increased length in normal females and normal males. Serum Ca was unaffected by ovariectomy, but orchiectomy resulted in decreased levels. Estradiol reduced serum Ca in gonadectomized animals; serum Ca was increased by estradiol treatment in intact females. Changes in tibial bone weight, ash weight and mineral composition, and relative sizes of epiphyseal and metaphyseal bone were gender-, gonadectomy- and hormone-specific. Bone weight was greater in ovariectomized mice. Ash weight per bone was comparable, but there was an increase in Ca and P content with ovariectomy. Estradiol increased bone weight, ash content, and bone Ca and P in ovariectomized and intact females. Orchiectomy alone did not alter bone weight, ash content, or Ca and P, but orchiectomized mice were sensitive to estradiol; all parameters were increased in the orchiectomized animals treated with estradiol. Analysis of the ash content and Ca and P per mg bone, rather than per bone, demonstrated estradiol and testosterone alter net bone formation, but not the amount of mineral per unit bone. Ovariectomy increased hypertrophic cartilage. While estradiol did not alter tibial area in ovariectomized mice, it caused an increase in intact females. The total amount of growth plate cartilage in ovariectomized animals was decreased by estradiol to levels typical of intact animals due to a greater decrease in the hypertrophic cartilage in the ovariectomized mice, as well as a greater increase in metaphyseal bone area. Testosterone had no effect on these parameters in the females. Orchiectomy decreased the amount of growth plate cartilage, but increased the hypertrophic zone. Estradiol increased growth plate cartilage in intact male mice, but decreased it in orchiectomized mice. This difference was also seen in the hypertrophic zone. Total growth plate cartilage and hypertrophic cartilage were increased by testosterone in intact males, whereas metaphyseal and epiphyseal bone area were decreased. The results show for the first time that there is a gender-specific response in both male and female mice to both estradiol and testosterone, whether or not the animals have been gonadectomized. For many parameters, orchiectomized mice behave like females in response to both sex steroids, indicating that the male gonad is needed for mouse bone to exhibit the male phenotypic response to estradiol and testosterone.     

Effects of gonadectomy and steroid treatment on renal prostaglandin 9-ketoreductase activity in the rat

The effect of gonadectomy and treatment with sex-steroids on renal prostaglandin 9-ketoreductase activity in 10-11 week old male and female rats was determined. Rats were gonadectomized or subjected to sham operation at 3 weeks of age. During week 7, rats were injected s.c. twice over a 6-day interval with vehicle (peanut oil, 0.5 ml X kg-1) or with depot forms of testosterone (5 mg X kg-1), estradiol (0.02 mg X kg-1), progesterone (5 mg X kg-1), or estradiol and progesterone combined. Renal prostaglandin 9-ketoreductase activity was about 50% higher in female rats than in males. Gonadectomy decreased 9-ketoreductase activity in females, but not in males, and eliminated the gender difference in enzyme activity. Treatment with estradiol elevated 9-ketoreductase activity in males and females, while treatment with testosterone or progesterone was without effect. Progesterone did, however, antagonize the elevation in 9-ketoreductase activity produced by estradiol.     

Immunological mediation of gonadal effects on experimental murine cysticercosis caused by Taenia crassiceps metacestodes.

Female BALB/c mice are naturally more susceptible than males to intraperitoneal experimental infection with Taenia crassiceps metacestodes. Gonadectomy tends to equalize susceptibility between sexes by reducing in half the mean individual intensity of females and by tripling that of males. The effect of gonadectomy is seen only in mice with intact immune systems but not in irradiated mice. Purified sex hormones (17-beta estradiol, testosterone, and progesterone) do not affect cysticercus reproduction or growth in vitro. Thus, gonadal effect on mouse susceptibility to cysticercosis appears to be mediated via the immune system, and it is probably not the consequence of the major sex steroids acting directly upon the parasites. Because sublethal irradiation increases the intensity in gonadectomized females and intact males, whereas that of gonadectomized males and intact females remains unchanged, irradiation results are consistent with the hypothesis that immunological events that participate in controlling the growth of cysticerci are inhibited by ovaries and stimulated by testes.     

Sex dimorphism of the interhemispheric asymmetry in the control of pain vocalizations in rats

First impulses were studied of pain vocalizations, elicited by electrostimulation of the tail root of semirigidly fixed 105 male and 95 female white rats of Wistar line. The rats were divided into three groups: with intact brain, with inactivated cortex of the left hemisphere and with inactivated cortex of the right one. It is shown, that as a result of unilateral decortication both in males and females changes take place in the character of durations distribution and probability of manifestation, as well as a reduction of the latency and an increase of peak amplitude of the recorded impulses. It is important that both in male and female rats the consequences of the left and right hemispheres inactivation differ by the influence on the character of durations distribution, probability of manifestation and the latency of pain vocalizations. At the same time, in males functional interhemispheric asymmetry of the control of probability of pain cries manifestation and latencies of pain squeals is more expressed than in females.     

Interhemispheric asymmetry of neocortex and hippocampus in orienting exploratory behavior of rabbits

Correlation of discharges of cortical neurons in symmetrical points of the visual and parietal cortices and left and right hippocampal CA1 neurons was studied in freely moving rabbits during exposure to emotional stimuli. Crosscorrelation histograms were plotted. As compared to the initial state, during an active orienting exploratory reaction to stimuli, the left-side influence on right-hemispheric cortical neurons with a delay about 100 ms increased, which led to asymmetry in interhemispheric interaction with the left-side dominance. During freezing, the left-side influence became weaker, and the effects of the right hemisphere prevailed. Hippocampal asymmetry in neuronal activity was in reciprocal relationship with neocortical asymmetry. In the hippocampus, the right-side influence with a delay about 200 ms increased during the active exploratory reactions resulting in the right-side dominance. Freezing was accompanied by strengthening of the left-side influence (the left-side dominance). During the active locomotion, neuronal interaction in the hippocampus was predominantly realized in the theta-range frequency, whereas freezing was characterized by the delta-range correlation. It was concluded that the active or passive nature of a behavioral reaction to emotional stimuli was correlated with changes in asymmetry in the interhemispheric neuronal interactions at the cortical and hippocampal levels.     

Lack of gonadal control of the dorsal gland and sandbathing in male and female bannertail kangaroo rats (Dipodomys spectabilis)

Previous studies have demonstrated gonadal control of mammalian scent glands; castration leads to reduced scent-marking rates and smaller gland sizes. I investigated whether gonadal hormones control the size of the dorsal gland (a specialized sebaceous gland) and sandbathing as a scent-marking behavior in adult male and female bannertail kangaroo rats (Dipodomys spectabilis). Gland sizes of males and females were similar in all age classes, except adult males with larger body weights had proportionately larger glands than females. Male gland sizes declined 18% following castration but were not significantly smaller than those of intact males; females showed no change in dorsal gland size either as a result of ovariectomy or after estradiol benzoate implants. Sandbathing rates also did not decline as a result of gonadectomy. Rather, castrated males and overiectomized females sandbathed at higher frequencies than intact males and ovariectomized females with estradiol benzoate implants, respectively. Gonadal hormones apparently have little influence on the function of a specialized scent gland and may inhibit sandbathing as a scent-marking behavior in adult D. spectabilis.     

Effects of gonadotropin-releasing hormone administration on the pituitary-gonadal axis in male and female dogs before and after gonadectomy

GnRH-stimulation tests were performed in 14 female and 14 male client-owned dogs of several breeds, before and 4 to 5 mo after gonadectomy. The aim of the study was to obtain more insight into the pituitary-gonadal axis in intact and neutered dogs and to establish reference values. Basal plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations were increased significantly after gonadectomy in both bitches and male dogs. In both males and females ranges of the basal plasma FSH concentrations, before and after gonadectomy, did not overlap as opposed to the overlap in ranges of the basal plasma LH concentrations. Before gonadectomy basal plasma LH concentrations were lower and basal plasma FSH concentrations were higher in bitches than in male dogs. After gonadectomy these basal values did not differ significantly. GnRH administration before gonadectomy resulted in an increase in plasma LH and FSH concentrations in both genders. GnRH administration after gonadectomy produced an increase only in plasma LH concentrations in both genders, and a just significant increase in plasma FSH in castrated male dogs. GnRH administration before gonadectomy resulted in a significant increase in plasma testosterone concentration in both genders. In males ranges of basal and GnRH-stimulated plasma testosterone concentrations before and after gonadectomy did not overlap. Basal plasma estradiol concentrations were significantly higher in intact males than in castrated males and their ranges did not overlap. The basal estradiol concentrations in bitches before and after ovariectomy were not significantly different. At 120 min after GnRH administration, ranges of plasma estradiol concentration of intact and ovariectomized bitches no longer overlapped. In conclusion, basal plasma FSH concentration appears to be more reliable than basal plasma LH concentration for verification of neuter status in both male and female dogs. The basal plasma testosterone concentration appears to be reliable for verification of neuter status in male dogs. The plasma estradiol concentration at 120 min after GnRH administration can be used to discriminate between bitches with and without functional ovarian tissue.     

Supraphysiological testosterone enanthate administration prevents bone loss and augments bone strength in gonadectomized male and female rats

High-dose testosterone enanthate (TE) may prevent hypogonadism-induced osteopenia. For this study, 3-mo-old male and female Fisher SAS rats underwent sham surgery, gonadectomy (GX), or GX plus 28 days TE administration (7.0 mg/wk). GX reduced serum sex hormones (i.e., testosterone, dihydrotestosterone, and estradiol) (P < 0.05) in both sexes and bone concentrations of testosterone (males only), and estradiol (females only). GX also elevated urine deoxypyridinoline/creatinine in both sexes and serum osteocalcin (females only), findings that are consistent with high-turnover osteopenia. GX reduced cancellous bone volume (CBV) and increased osteoid surfaces in tibia of both sexes. GX males also experienced reduced trabecular number and width and increased trabecular separation, whereas GX females experienced increased osteoblast and osteoid surfaces. Bone biomechanical characteristics remained unaffected by GX, except that femoral stiffness was reduced in females. In contrast, TE administration to GX rats elevated serum and bone androgens to supraphysiological concentrations in both sexes but altered neither serum nor bone estradiol in males. Additionally, TE did not prevent GX-induced reductions in serum or bone estradiol in females. TE also reduced markers of high-turnover osteopenia in both sexes. In males, TE prevented GX-induced changes in trabecular number and separation, CBV, and osteoid surfaces while diminishing osteoblast and osteoclast surfaces; however, these changes were not fully prevented in females. In both sexes, TE increased femoral length and femoral maximal strength to above that of Sham and GX animals while preventing the loss of femoral stiffness in females. In conclusion, TE administration appears protective of cancellous bone in male rats and augments cortical bone strength in both sexes.     

Effects of gonadectomy and sex hormones on the levels of noradrenaline and dopamine in rat hypothalamus

The levels of noradrenaline and dopamine were determined in the homogenates of the hypothalamus of rats of either sex. The determinations were done in intact rats, after sham gonadectomy, 6 and 9 weeks after gonadectomy, and in gonadectomized rats receiving 6 weeks after gonadectomy one dose of oestradiol cypionate (females) or testosterone cypionate (males). Catecholamines were determined fluorimetrically. The changes of the determined catecholamines differed in the hypothalamic homogenates in males and females after gonadectomy. Following orchidectomy the noradrenaline level rose, while after ovariectomy the level of this catecholamine decreased. Contrary to this, in ovariectomized rats the dopamine level was significantly raised after the operation. This change was reversible as observed after administration of oestradiol cypionate. Orchidectomy and testosterone cypionate injection had no effect on the dopamine level in the hypothalamus. The role of these catecholamines in the processes connected with the regulation of the hypothalamus-hypophysis-gonad axis is discussed.     

Sex steroid hormones enhance immune function in male and female Siberian hamsters

Immune function is better in females than in males of many vertebrate species, and this dimorphism has been attributed to the presence of immunosuppressive androgens in males. We investigated the influence of sex steroid hormones on immune function in male and female Siberian hamsters. Previous studies indicated that immune function was impaired in male and female hamsters housed under short-day photoperiods when androgen and estrogen concentrations were virtually undetectable. In experiment 1, animals were gonadally intact, gonadectomized (gx), or gx with hormone replacement. Females exhibited the expected increase in antibody production over males, independent of hormone treatment condition, whereas male and female gx animals exhibited decreased lymphocyte proliferation to the T cell mitogen, phytohemagglutinin (PHA) compared with intact animals, and this effect was reversed in gx hamsters following testosterone and estradiol treatment, respectively. In experiment 2, testosterone, dihydrotestosterone, and estradiol all enhanced cell-mediated immunity in vitro, suggesting that sex steroid hormones may be enhancing immune function through direct actions on immune cells. In experiment 3, an acute mitogen challenge of lipopolysaccharide significantly suppressed lymphocyte proliferation to PHA in intact males but not females, suggesting that males may be less reactive to a subsequent mitogenic challenge than females. Contrary to evidence in many species such as rats, mice, and humans, these data suggest that sex steroid hormones enhance immunity in both male and female Siberian hamsters.     

Ovarian hormones after postnatal day 20 reduce neuron number in the rat primary visual cortex

Previous work from our lab has documented a sex difference in neuron number in the binocular region of the adult rat primary visual cortex (Oc1B), with males having 19% more neurons than females. In the present study, the role of developmental steroid hormones in the formation of this difference was explored. Male and female rats underwent neonatal hormone manipulation (female + testosterone or dihydrotestosterone; male + flutamide) followed by gonadectomy on postnatal day 20. Animals that did not undergo hormone manipulation were either gonadectomized or sham operated at day 20. Neuron number was quantified in the monocular (Oc1M) and binocular (Oc1B) subfields of the adult rat primary visual cortex using the optical disector technique. As adults, day 20 gonadectomized females, as well as females + testosterone and females + dihydrotestosterone, had significantly more neurons than intact females. There was no difference in neuron number between postnatal day 20 gonadectomized males, males + flutamide, and intact males. Also, intact males had significantly more neurons than intact females in both in Oc1M and Oc1B. It appears that ovarian steroids after day 20 are the primary cause of the lower number of neurons in the primary visual cortex of the female rat.     

Asymmetry of the cerebral hemispheres during comparison of paired visual stimuli

In conditions of tachistoscopic presentation of visual stimuli, healthy (male and female) right-handed subjects carried out a paired comparison of the stimuli presented unilaterally and in the center of the visual field. In case of recognition of images of words and objects, the number of correct answers and motor reaction time usually did not significantly differ at two interstimuli intervals (1 and 10 s). In comparing images of faces, there also were no differences by the number of reactions, and the reaction time was less at the intervals of 1 s. The left hemisphere dominated at the identification of words and female faces, the right one--at the recognition of male faces. When the right visual field was stimulated images of various classes were recognized more differentially than at the stimulation of the left visual field. The male subjects had more prominent interhemispheric differences than the females. The increase of the interstimuli interval from 1 to 10 s brought to a weakening of the functional interhemispheric asymmetry and decreasing of the differences between the male and female subjects. The obtained data show that in the processes connected with short-time memory, functional interhemispheric asymmetry is basically formed at the initial stages of the information processing.