Sex differences in brain developing in the presence or absence of gonads

Brain sexual differentiation results from the interaction of genetic and hormonal influences. This study used a unique agonadal mouse model to determine relative contributions of genetic and gonadal hormone influences in the differentiation of selected brain regions. SF-1 knockout (SF-1 KO) mice are born without gonads and adrenal glands and are not exposed to endogenous sex steroids during fetal/neonatal development. Consequently, male and female SF-1 KO mice are born with female external genitalia and if left on their own, die shortly after birth due to adrenal insufficiency. In this study, SF-1 KO mice were rescued by neonatal adrenal transplantation to examine their brain morphology in adult life. To determine potential brain loci that might mediate functional sex differences, we examined the area and distribution of immunoreactive calbindin and neuronal nitric oxide synthase in the preoptic area (POA) and ventromedial nucleus of the hypothalamus, two areas previously reported to be sexually dimorphic in the mammalian brain. A sex difference in the positioning of cells containing immunoreactive calbindin in a group within the POA was clearly gonad dependent based on the elimination of the sex difference in SF-1 KO mice. Several other differences in the area of ventromedial hypothalamus and in POA were maintained in male and female SF-1 KO mice, suggesting gonad-independent genetic influences on sexually dimorphic brain development.     

Long-term studies on compensatory adrenal growth in the female hamster induced by unilateral adrenalectomy

The study was designed to explain the cellular aspects of compensatory adrenal growth in the female hamster in the course of long-term unilateral adrenalectomy. Animals were autopsied 3, 6, 9, 18 and 36 days after unilateral adrenalectomy. Removal of the left adrenal gland within 36 days did not change both the absolute and relative adrenal gland weight of the female hamster. Also the volume of particular adrenocortical zones and the number of parenchymal cells in the zones and in the entire cortex were unchanged in unilaterally adrenalectomised hamsters. Moreover, in the course of experiments the volumes of the glomerulosa and fasciculata cells were unchanged in relation to the control group. On the contrary, a marked increase in the volume of the zona reticularis cells was observed, with the highest rate of increase within the first 9 days after unilateral adrenalectomy.     

Deoxyglucose-autoradiography of the hypothalamus after food deprivation in the mouse

[14C] deoxyglucose-autoradiography of mouse brain after food deprivation showed no specific changes in the ratio of autoradiographic optical density of the lateral nucleus of the hypothalamus (LH) versus ventromedial nucleus of the hypothalamus (VMH). The results show that even if there were differences in functional activity between these hypothalamic nuclei during conditions of hunger and satiety, they are not reflected as autoradiographically detectable in relative deoxyglucose uptake.     

Study of electrical activity in the area of the hypothalamic ventromedial nucleus and the lateral hypothalamus of rats fed on a high protein and high fat diet.

The authors studied bioelectric potentials in the area of the hypothalamic ventromedial nucleus and the lateral hypothalamus of rats fed on a standard, a high protein and a high fat diet. On the first 3--6 days after changing from the standard to the high fat and high protein diets, a decrease in the amplitude of electrical activity was recorded in both the areas in question. It was also found that the frequency of electrical activity in the hypothalamic ventromedial nucleus or the lateral hypothalamus rose, after 3 days administration of the high fat or the high protein diet, in correlation to the type of diet, and that, in the frequency spectrum, a change occurred in the proportion of basic frequency in relation to superimposed frequencies distorting it. It was further found that there was a permanent difference between the amplitude of electrical activity in the lateral hypothalamus and the hypothalamic ventromedial nucleus.     

Effects of adrenalectomy and nephrectomy on adrenal regeneration hypertension in the rat.

The involvement of the regenerating adrenal gland and kidney, and the contribution of deoxycorticosterone (DOC) and prostaglandin E2 (PGE2), in the development of adrenal regeneration hypertension (ARH) was evaluated in young female Sprague-Dawley rats. Based on tail-cuff plethysmographic measurement, animals subjected to nephrectomy and adrenalectomy on the right side and adrenal enucleation (removal of the adrenal cortex) on the left side developed significant (P less than 0.05, n = 12) hypertension within 6 weeks following operation. Subsequent left nephrectomy in these ARH rats produced a further elevation, whereas a secondary adrenalectomy resulted in an acute and discernible reduction in blood pressure within 24-36 hours. It is interesting to note that the progressive increase in blood pressure following left nephrectomy was significantly reversed by PGE2 (10 or 20 micrograms/kg, i.p.). At the same time, the reduction in blood pressure after secondary adrenalectomy was significantly retarded by deoxycorticosterone trimethylacetate (2 mg/kg, i.p.). These data demonstrated that both the kidney and the regenerating adrenal cortex are involved in the pathogenesis of ARH. Furthermore, it is probable that the secretion of DOC by the regenerating adrenal cortex is responsible for the elevation in blood pressure, in a process that is balanced by PGE2, possibly secreted by the kidney.     

Combination unilateral amygdaloid and ventromedial hypothalamic lesions: evidence for a feeding pathway

Previous studies have reported hyperphagia and obesity in female rats with bilateral lesions of the most posterodorsal part of the amygdala. In rats with unilateral posterodorsal amygdaloid lesions, a dense pattern of anterograde degeneration appears in the ipsilateral ventromedial hypothalamus, but not the contralateral nucleus. In the present study, female rats with unilateral ventromedial hypothalamic lesions or sham lesions were given either sham lesions or unilateral lesions of the posterodorsal amygdala (PDA) 20 days later. Unilateral lesions of the ventromedial hypothalamus resulted in hyperphagia and excessive weight gain. Subsequent amygdaloid lesions that were contralateral to the initial hypothalamic lesions resulted in hyperphagia and additional excessive weight gains, but amygdaloid lesions ipsilateral to the initial hypothalamic lesions did not. It is concluded that the effects of the two lesions on body weight are not additive and that the PDA and ventromedial hypothalamus are part of the same ipsilateral pathway regulating feeding behavior and body weight regulation.     

IGF1 and 2 in two models of adrenal growth

Insulin-like growth factors (IGFs) 1 and 2 were measured in the adrenal glands of rats undergoing either compensatory growth following left unilateral adrenalectomy or adrenal regeneration following bilateral adrenal enucleation. In normal rat adrenal gland, the tissue concentration of IGF2 (7.45 +/- 0.99 pg/micrograms protein) wa higher than IGF1 (1.26 +/- 0.23 pg/micrograms protein), both peptides being more abundant in the inner zones of the adrenal gland compared to the capsule-glomerulosa. During compensatory growth of the right adrenal gland, IGF1 and 2 increased significantly compared with control right adrenal glands at 24 h following left unilateral adrenalectomy (P less than 0.001). At 68 h, the increase remained significant for IGF1 (P = 0.012). The two peptides were measured in the regenerating adrenal gland at 7, 14 and 21 days following bilateral enucleation. Whilst there was a trend towards an increase in the IGF1 and 2 content of regenerating adrenal glands, the increase was significant only for IGF2 in the left adrenal gland at 21 days following enucleation. Plasma IGF1 and 2 did not increase compared to controls during the experiments (110.97 +/- 1.95 and 46.33 ng/ml, respectively), suggesting that the changes in tissue IGF reflect increased local production during rapid growth of the adrenal gland.     

Distribution of aromatase-immunoreactive cells in the mouse forebrain

Summary The distribution of aromatase-immunoreactive cells was studied by immunocytochemistry in the mouse forebrain using a purified polyclonal antibody raised against human placental aromatase. Labeled perikarya were found in the dorso-lateral parts of the medial and tuberal hypothalamus. Positive cells filled an area extending between the subincertal nucleus in the dorsal part, the ventromedial hypothalamic nucleus in the ventral part, and the internal capsule and the magnocellular nucleus of the lateral hypothalamus in the lateral part. The same distribution was seen in the two strains of mice that were studied (Jackson and Swiss), and the number of immunoreactive perikarya did not seem to be affected by castration or testosterone treatment. No immunoreactivity could be detected in the medial regions of the preoptic area and hypothalamus; these were expected to contain the enzyme based on assays of aromatase activity performed in rats and on indirect autoradiographic evidence in mice. Our data raise questions concerning the distribution of aromatase in the brain and the mode of action of the centrally produced estrogens.     

Sex and the Developing Brain: Suppression of Neuronal Estrogen Sensitivity by Developmental Androgen Exposure

The developmental effects of androgen play a central role in sexual differentiation of the mammalian central nervous system. The cellular mechanisms responsible for mediating these effects remain incompletely understood. A considerable amount of evidence has accumulated indicating that one of the earliest detectable events in the mechanism of sexual differentiation is a selective and permanent reduction in estrogen receptor concentrations in specific regions of the brain. Using quantitative autoradiographic methods, it has been possible to precisely map the regional distribution of estrogen receptors in the brains of male and female rats, as well as to study the development of sexual dimorphisms in receptor distribution. Despite previous data suggesting that the left and right sides of the brain may be differentially responsive to early androgen exposure, there is no significant right-left asymmetry in estrogen receptor distribution, in either sex. Significant sex differences in receptor density are, however, observed in several regions of the preoptic area, the bed nucleus of the stria terminalis and the ventromedial nucleus of the hypothalamus, particularly in its most rostral and caudal aspects. In the periventricular preoptic area of the female, highest estrogen receptor density occurs in the anteroventral periventricular region: binding in this region is reduced by approximately 50% in the male, as compared to the female. These data are consistent with the hypothesis that androgen-induced defeminization of feminine behavioral and neuroendocrine responses to estrogen may involve selective reductions in the estrogen sensitivity of critical components of the neural circuitry regulating these responses, mediated in part through a reduction in estrogen receptor biosynthesis.     

Autonomic and endocrine factors in the regulation of energy balance

The regulation of energy reserves is modified by both the autonomic nervous system and the hormonal milieu. The activity of the two limbs of the autonomic nervous system shows a reciprocal response to stimulation or damage in either the ventromedial or the lateral hypothalamus. Ventromedial hypothalamic lesions decrease the activity of the sympathetic nervous system and increase the activity of the vagus nerve. Lateral hypothalamic lesions, on the other hand, increase the activity of the sympathetic nervous system. Central neurotransmitters involved in energy balance include the monoamines, amino acids, and peptides. Removal of adrenal steroids by adrenalectomy reverses or attenuates all forms of obesity by reducing food intake and possibly by increasing energy expenditure. Acute insulin injections increase food intake, but chronic injections may reduce it. A model showing the reciprocal relation of sympathetic activity to energy reserves is presented.     

Rat insulin-like growth factor-I and -II mRNAs are unchanged during compensatory adrenal growth but decrease during ACTH-induced adrenal growth

The insulin-like growth factors (IGFs) may be important autocrine and paracrine mediators of organ growth. We used solution-hybridization/ribonuclease protection assays to examine IGF-I and IGF-II mRNA abundance during hypertrophy or the rat adrenal gland induced by unilateral adrenalectomy or by adrenocorticotropic hormone (ACTH) infusion. Adrenal IGF-I mRNA did not change during the period of rapid organ growth at 18 or 66 h after unilateral adrenalectomy. ACTH infusion induced a time- and dose-dependent decrease in adrenal IGF-I mRNA despite significant increases in gland size. IGF-II mRNA also remained unchanged after unilateral adrenalectomy and decreased after ACTH infusion, to a greater extent than IGF-I mRNA. Liver IGF-I mRNA did not change with ACTH exposure, indicating an effect specific to the adrenal. We also measured adrenal P450scc mRNA as a marker of steroidogenic capacity. P450scc mRNA was unchanged after unilateral adrenalectomy and increased with ACTH infusion. Thus IGF-I and IGF-II mRNAs respond in parallel, but in different fashions with different stimuli for adrenal growth. The decrease in IGF mRNA after exposure to ACTH may be a factor in the ACTH-induced inhibition of compensatory hypertrophy after unilateral adrenalectomy.     

The oculomotor nucleus, not the abducent, innervates the muscles which advance the nictitating membrane in birds

The topographic distribution of the neurones that innervate the muscles that advance the nictitating membrane in birds was studied using intra-axonal retrograde transport of horseradish peroxidase. The motor neurones are distributed in the oculomotor complex of the ipsilateral and contralateral sides. In the ipsilateral side, the neurones innervating the pyramidalis muscles were located in the dorsolateral, dorsomedial and ventromedial subnuclei, while those neurones innervating the quadratus muscle were found in the dorsomedial and dorsolateral subnuclei. In the contralateral side the neurones innervating both the pyramidalis and quadratus were distributed in the ventromedial and ventrolateral subnuclei. The sensory neurones were found in the trigeminal ganglion and trigeminal mesencephalic nucleus.     

The role of nigral projections to the thalamus in drug-induced circling behaviour in the rat

Unilateral injection of 6-hydroxydopamine (6-OHDA) into the ascending nigrostriatal pathway caused contraversive circling to apomorphine and ipsiversive circling to amphetamine respectively. An electrolesion of the ventromedial thalamic nucleus on the same side as the 6-OHDA lesion reduced apomorphine-induced circling, but not that to amphetamine. An electrolesion of the ventromedial thalamic nucleus on the side opposite to the 6-OHDA lesion reduced amphetamine circling but not that to apomorphine. Bilateral electrolesions of the ventromedial thalamic nucleus reduced neither apomorphine- nor amphetamine-induced circling. Electrolytic lesions of the parafascicular thalamic nucleus did not reduce apomorphine- or amphetamine-induced circling in animals with a unilateral 6-OHDA lesion of the nigrostriatal pathway. Knife cuts rostral and dorsal to the substantia nigra did not attenuate circling induced by injection of muscimol into the substantia nigra. Circling due to activition of nigral output pathways can be mediated by descending nigro-reticular pathways.     

结节乳头体在小鼠运动和摄食中的作用及机制研究

目的:探讨结节乳头体在小鼠运动和摄食中的作用及机制。方法:选择雄性ddy小鼠,180-200 g,通过单侧植入电极损毁TMN-E2区。采用荧光金逆行追踪方法检测小鼠Me5与TMN之间的神经纤维联系;采用免疫组化方法检测小鼠TMN中组氨酸脱羧酶(HDC)免疫反应阳性细胞数;采用旷场试验箱记录小鼠全天、夜间以及白天的自主活动和摄食摄水;采用PCR检测小鼠穹窿周和下丘脑外侧区的orexin m RNA的表达。结果:荧光金逆行追踪实验显示小鼠Me5可向TMN-E2发出神经纤维投射。单侧TMN损毁,两侧TMN中HDC反应阳性细胞显著减少(P0.05),且损毁侧比未损毁侧HDC免疫反应阳性细胞数减少(P0.05)。TMN损毁对小鼠24 h自主活动和摄食摄水无明显影响。单侧TMN损毁,小鼠从暗期到光期的自主活动和摄食摄水显著减少(P0.05)。单侧TMN损毁,小鼠正常昼夜活动摄食节律无显著改变。单侧TMN损毁,小鼠穹隆周和下丘脑外侧区白天的orexin m RNA表达显著减少(P0.05)。结论:Me5与TMN之间存在神经通路,该通路可能通过调节穹隆周区或下丘脑外侧区的orexin神经元的激活从而调控摄食及相关行为的昼夜节律。     

Epinephrine-independent production of hyperuricemia by means of hypothalamic stimulation in the conscious rat

The electrical stimulation of the ventromedial hypothalamus with 0.6 mA current produced an acute hyperuricemia associated with a rise in plasma allantoin in the conscious rat. Adrenal demedullation did not depress the hyperuricemic response. Even after the demedullation, neither propranolol nor phentolamine had any significant effects as well. These results indicate that endogeneous catecholamines are not involved in the production of the hyperuricemia; this is in sharp contrast with our previous result demonstrating the development of hyperuricemia via adrenal epinephrine by stimulating the ventromedial nucleus with 0.2 mA current. It is concluded therefore that ventromedial hypothalamic stimulation is capable of producing two different types of hyperuricemia, i.e. adrenal-epinephrine-dependent and epinephrine-independent, by varying the intensity of the stimulation current.     

Vagal influence on the adrenocortical function of the rat

The vagal influence on the fasciculata's function was studied in 23 Wistar male rats. The corticoadrenal function was evaluated by means of karyometric and histological studies. After vagotomy, the fasciculata of the left adrenal (operated side) showed a significant increase of the nuclear area in comparison with the right (control) side. This side difference was maintained in the stressed rats. In these animals the nuclear area did not increase significantly in either of the two adrenals. These results lead to the following conclusions: the vagus nerve, in normal conditions, has an inhibitory influence on the adrenal cortex; the vagal participation in the corticoadrenal response to a neurogenic stressor is meagre; the inhibitory vagal action on the fasciculata must be direct since the corticoadrenal modifications were unilateral, whereas, if the vagal influence were exerted through the hypophysis, the adrenal reaction should be bilateral; and, finally, the participation of the vagus nerve in the adrenal vascular disorders, which appeared in the stressed rats, seems to be insignificant since both glands, vagotomized and non vagotomized, showed a similar appearance.     

Glucagon-related peptides in the rat hypothalamus

Summary Immunohistochemically, nerve fibers and terminals reacting with anti-N-terminal-specific but not with anti-C-terminal-specific glucagon antiserum were observed in the following rat hypothalamic regions: paraventricular nucleus, supraoptic nucleus, anterior hypothalamus, arcuate nucleus, ventromedial hypothalamic nucleus and median eminence. Few fibers and terminals were demonstrated in the lateral hypothalamic area and dorsomedial hypothalamic nucleus. Radioimmunoassay data indicated that the concentration of gut glucagon-like immunoreactivity was higher in the ventromedial nucleus than in the lateral hypothalamic area. In food-deprived conditions, this concentration increased in both these parts. This was also verified in immunostained preparations in which a marked enhancement of gut glucagon-like immunoreactivity-containing fibers and terminals was observed in many hypothalamic regions. Several immunoreactive cell bodies were found in the ventromedial and arcuate nuclei of starved rats. Both biochemical and morphological data suggest that glucagon-related peptides may act as neurotransmitters or neuromodulators in the hypothalamus and may be involved in the central regulatory mechanism related to feeding behavior and energy metabolism.     

国人分裂颧骨的观察

观察了200个成人颅骨,不完全二分颧骨的出现率最高,完全二分颧骨次之,三分颧骨最少。不完全二分颧骨各缝的出现率不同,其中以后水平缝多见,前水平缝次之,全水平缝更少。本文还对该骨出现的成因进行了探讨。     

Stress-Related Changes in Cerebral Catecholamine and Indoleamine Metabolism: Lack of Effect of Adrenalectomy and Corticosterone

The concentrations of catecholamine and indoleamine metabolites were measured in intact and adrenalectomized mice to determine whether adrenal hormones mediate or modulate the stress-induced responses. Thirty minutes of footshock resulted in significant increases of the ratios of the dopamine (DA) catabolite, dihydroxyphenylacetic acid (DOPAC), to DA in prefrontal cortex, nucleus accumbens, striatum, hypothalamus, and brainstem, and of homovanillic (HVA)/DA ratios in nucleus accumbens, striatum, amygdala, and hypothalamus. Ratios of 3-methoxy-4-hydroxyphenylethyleneglycol to norepinephrine (NE) were also increased in prefrontal cortex, nucleus accumbens, septum, amygdala, hypothalamus, hippocampus, and brainstem. The concentration of NE was decreased in amygdala. 5-Hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT, serotonin) ratios and free tryptophan were also increased in every brain region. Very similar data were obtained from mice restrained for 30 min. Adrenalectomy resulted in increased HVA/DA ratios in prefrontal cortex and striatum, and 5-HIAA/5-HT in septum. The stress-related changes were largely similar in adrenalectomized mice. Significant interactions between adrenalectomy and footshock treatment occurred in prefrontal cortical DOPAC/DA and hypothalamic NE which was depleted only in adrenalectomized mice, suggesting tendencies for these measures to be more responsive in adrenalectomized mice. Corticosterone administration (0.5-2.0 mg/kg s.c.) which resulted in plasma concentrations in the physiological range did not alter the concentrations of the cerebral metabolites measured in any region. We conclude that adrenal hormones do not mediate cerebral catecholamine or indoleamine metabolism in stress, although adrenalectomy may affect HVA and 5-HIAA metabolism, and there was a tendency for catecholamines to be more sensitive to stress in adrenalectomized animals.     

Asymptomatic Bilateral Giant Adrenal Myelolipomas: Case Report and Review of Literature

ObjectiveTo describe an unusual case of bilateral giant adrenal masses caused by a primary adrenal myelolipoma.MethodsWe present the clinical, laboratory, and pathologic findings in a 32-year-old man with bilateral adrenal masses. The previous reports of bilateral myelolipomas also were reviewed.ResultsDuring a routine examination, a 32-year-old Thai man was found to have an asymptomatic abdominal mass. A computed tomographic scan of the abdomen disclosed bilateral adrenal masses; the one on the left was approximately 27 by 24 by 12 cm, and the one on the right side was 9 by 5 by 5 cm. The computed tomographic scan characteristics showed that both masses consisted mainly of low-density tissues (-30 to -90 Hounsfield units), suggestive of fatty component. An endocrinologic evaluation revealed no evidence of adrenal cortical or medullary functional abnormalities. Bilateral adrenalectomy was performed because of the large size of the lesions and the inability to rule out malignant involvement.ConclusionMyelolipoma is a relatively rare benign tumor of the adrenal glands composed of adipose cells and mature hematopoietic elements. Most such lesions are small, asymptomatic, and unilateral; giant or bilateral myelolipomas are quite rare. To our knowledge, our current case may represent the largest bilateral lesions in the literature. (Endocr Pract. 2007;13:667-671)