scholarly journals Brain-synthesized estrogens regulate cortical migration in a sexually divergent manner

2019 ◽  
Author(s):  
Katherine J. Sellers ◽  
Matthew C.S. Denley ◽  
Atsushi Saito ◽  
Atsushi Kamiya ◽  
Deepak P. Srivastava

AbstractEstrogens play an important role in the sexual dimorphisms that occur during brain development, including the neural circuitry that underlies sex-typical and socio-aggressive behaviors. Aromatase, the enzyme responsible for the conversion of androgens to estrogens, is expressed at high levels during early development in both male and female cortices, suggesting a role for brain-synthesized estrogens during corticogenesis. This study investigated how the local synthesis of estrogens affects neurodevelopment of the cerebral cortex, and how this differs in males and females by knockdown expression of the Cyp19a1 gene, which encodes aromatase, between embryonic day 14.5 and postnatal day 0 (P0). The effects of Cyp19a1 knockdown on neural migration was then assessed. Aromatase was expressed in the developing cortex of both sexes, but at significantly higher levels in male than female mice. Under basal conditions, no obvious differences in cortical migration between male and female mice were observed. However, knockdown of Cyp19a1 increased the number GFP-positive cells in the cortical plate, with a concurrent decrease in the subventricular zone/ventricular zone in P0 male mice. The opposite effect was observed in females, with a significantly reduced number of GFP-positive cells migrating to the cortical plate. These findings have important implications for our understanding of the role of fetal steroids for neuronal migration during cerebral cortex development. Moreover, these data indicate that brain-synthesized estrogens regulate radial migration through distinct mechanisms in males and females.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yu Hasegawa ◽  
Shin-Yu Chen ◽  
Lili Sheng ◽  
Prasant Kumar Jena ◽  
Karen M. Kalanetra ◽  
...  

Abstract Long-term consumption of a diet with excessive fat and sucrose (Western diet, WD) leads to an elevated risk of obesity and metabolic syndrome in both males and females. However, there are sexual dimorphisms in metabolism which are apparent when considering the prevalence of complications of metabolic syndrome, such as non-alcoholic fatty liver disease. This study aimed to elucidate the impact of a WD on the metabolome and the gut microbiota of male and female mice at 5, 10, and 15 months to capture the dynamic and comprehensive changes brought about by diet at different stages of life. Here we show that there are important considerations of age and sex that should be considered when assessing the impact of diet on the gut microbiome and health.


2017 ◽  
Vol 152 (5) ◽  
pp. S212
Author(s):  
Muriel H. Larauche ◽  
Nabila Moussaoui ◽  
Mandy Biraud ◽  
Won Ki Bae ◽  
Wendy Walwyn ◽  
...  

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Jessica L Faulkner ◽  
Eric J Belin de Chantemele

Recent studies by our group demonstrated that leptin is a direct regulator of aldosterone secretion and increases blood pressure via sex-specific mechanisms involving leptin-mediated activation of the aldosterone-mineralocorticoid receptor signaling pathway in females and sympatho-activation in males. Although it is well accepted that females secrete more leptin and aldosterone than males, it is unknown whether leptin infusion raises blood pressure similarly in male and female mice and whether higher aldosterone levels sensitize females to salt-induced hypertension. We hypothesized that female mice would be more sensitive to leptin than males and also have a potentiated blood pressure rise in response to high salt diet compared to males. Male and female Balb/C mice were implanted with radiotelemeters for continuous measurement of mean arterial pressure (MAP) at 10 weeks of age. MAP was measured for seven days prior to feeding with a high-salt diet (HS, 4%NaCl) for seven days. Following a recovery period, animals were then implanted with osmotic minipumps containing leptin (0.9mg/kg/day) recorded for seven days. Baseline MAP was similar between males and females (101.3±2.9 vs 99.3±3.7 mmHg, n=4 and 5, respectively), however, HS diet resulted in a greater MAP increase in females (15.0±2.6 mmHg) compared to males (3.1±4.5 mmHg, P<0.05). MAP with leptin treatment was increased with leptin in females moreso than in males, however, this did not reach significance (6.8±5.8 vs 1.8±5.9 mmHg, respectively). This potential sex difference in blood pressure responses to leptin was not associated with changes in body weight (0.07±0.44 vs -0.22±0.2 g, respectively) nor changes in blood glucose (-19.67±15.06 vs -15.4±11.4 mg/dl, respectively) in males and females in response to leptin. In summary, female mice are more sensitive to HS diet-induced blood pressure increases than males. Females may be more sensitive to leptin-mediated blood pressure increases than males. Further investigation is needed to determine whether these sex differences in blood pressure responses to HS diet and leptin are mediated by aldosterone or other mechanisms.


Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Quaisar Ali ◽  
Yonnie Wu ◽  
Tadashi Inagami ◽  
Tahir Hussain

Angiotensin II acting via Angiotensin II type 2 receptors (AT2Rs) is believed to be protective against blood pressure increase and affects renal function under pathophysiological condition. Recently we have observed that stimulation of AT2Rs in male obese Zucker rats has shifted the two opposing arms of renin angiotensin system (RAS) i.e. ACE-Ang II-AT1 vs ACE2/Ang-(1-7)-Mas. Evidence suggests that estrogen regulates RAS, including AT2R in female mice. We hypothesized that AT2R has a gender specific regulation of RAS. In the present study, we investigated the role of AT2Rs in regulating RAS components in male and female mice. Kidney cortex from AT2R knockout (AT2RKO) male and female mice and wild type (WT) with similar background (C57BL/6) of 20 weeks of age were used in the study. The cortical ACE expression (ng ACE/μg tissue) was significantly increased in AT2RKO mice (3±0.02) compared to WT males (1.9±0.02). LC/MS analysis of cortical tissue revealed that Ang II was also significantly increased in AT2RKO mice (WT: 31±3, AT2RKO: 47±3 fmoles/mg tissue). Deletion of AT2R significantly increased AT1R (204%, 204 of 100) expression and had no effect on renin activity compared to WT males. The cortical expression of ACE2 activity (WT: 113±8, AT2RKO: 40±11, RFU/min), Ang-(1-7) levels (WT: 7.3±1.4, AT2RKO: 3±0.8 fmoles/mg tissue) and Mas receptor (AT2RKO: 54±15, % of WT) was significantly decreased in AT2RKO males compared to WT. The cortical expression of the AT2R and MasR was 2-fold greater in WT females compared to WT male. The renin activity (WT: 32±2, AT2RKO: 21±0.3, RFU/min) and MasR expression (WT: 187.5±55, AT2KO: 47±9) was significantly decreased in AT2RKO females compared to the female WT. Interestingly, Ang-(1-7) level (WT: 5.7±0.7, AT2RKO 2.6±0.7 fmoles/mg tissue) was decreased but no changes in ACE or ACE2 activity was observed in AT2KO females compared to their WT, suggesting a role of non-ACE2 pathway. This study suggests that AT2R regulates ACE/ACE2 ratio-Ang II-AT1R expression negatively only in males, whereas in females, it regulates Ang-(1-7) potentially via non-ACE2 pathway. Such changes indicate a gender specific mechanisms potentially associated with AT2R-mediated regulation of renal function and blood pressure control.


2011 ◽  
Vol 143 (3) ◽  
pp. 245-253 ◽  
Author(s):  
Christelle Guédot ◽  
David R. Horton ◽  
Peter J. Landolt

AbstractWe examined the role of chemical signals in sex attraction of pear psylla, Cacopsylla pyricola (Förster), assessing the response of summerform male and female psyllids to male- and female-produced volatile chemicals. Male psyllids were attracted to odors from live females and pentane extracts of females. Extracts of females were as attractive to males as live females, suggesting that the female-produced volatile chemicals responsible for male attraction might be isolated by extracting females with pentane. Females were not attracted to odorants from live females and tended to avoid odorants from extracts of females. Furthermore, summerform males and females were not attracted or repelled by male-produced odorants from live males or extracts of males. Results of olfactometer assays using male summerform C. pyricola are consistent with results from earlier studies with the winterform morphotype of this species.


1991 ◽  
Vol 11 (2) ◽  
pp. 292-298 ◽  
Author(s):  
Edward D. Hall ◽  
Kay E. Pazara ◽  
Kelley L. Linseman

Twenty-four hour postischemic neuronal necrosis was compared in male vs. female Mongolian gerbils subjected to a 3-h period of severe incomplete hemispheric ischemia produced by unilateral carotid occlusion. The incidence of stroke-prone males was 42.9% versus 26.7% for the females. Among the stroke-prone animals, the males displayed significantly greater neuronal necrosis at 24 h after ischemia compared to the females in the cerebral cortex and CA, region of the hippocampus. In the CA, region of the stroke-prone males, only 2.0% of the normal neuronal population remained by 24 h compared to 36.8% in the stroke-prone females (p < 0.02). In the cerebral cortex, the males had only 19.9% of normal versus 58.2% in the females (p < 0.05). In a second series of mechanistic experiments, no differences in cortical blood flow (CBF) were disclosed between preselected male and female stroke-prone animals before, during, or for 2 h after ischemia. As with the CBF, the extent of cortical extracellular hypocalcia during ischemia did not differ significantly. However, the degree of postischemic recovery of cortical extracellular calcium was significantly better in the females from 30 min to 2 h after reperfusion. In the same experiments, hemispheric vitamin E levels were measured at the 2 h time point as an index of postischemic brain lipid peroxidation. No difference in baseline vitamin E levels was observed between male and female sham-operated gerbils. In the males subjected to 3 h of ischemia plus 2 h of reperfusion, the hemispheric vitamin E decreased by 43.5% compared to the sham-operated males. In contrast, the females displayed only a 4.2% decline (p < 0.05 versus males). Previous studies showing the protective efficacy of antioxidants in this model have suggested an important role of oxygen radical-induced lipid peroxidation. Thus, it is proposed that the lesser ischemic vulnerability of females may be based upon an antioxidant effect of endogenous estrogen. Indeed, estrogen was found to be a more potent inhibitor of iron-catalyzed lipid peroxidation in brain tissue than vitamin E.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
L Grimbert ◽  
M N Sanz ◽  
C Rucker-Martin ◽  
M Novotova ◽  
M Gressette ◽  
...  

Abstract Introduction Mitochondrial dysfunction plays a major role in the Heart Failure (HF) pathophysiology.The AMP activated protein kinase (AMPK) is activated by a high AMP-ADP/ATP ratio and regulates a number of metabolic pathways. Many studies have highlighted a protective role of AMPK in HF, but its relevance to cardiac tissue, its metabolic part and its sex specificity are not well established. Purpose Then, the aim of this study is to determine the role of AMPK in the healthy and failing heart in male and female mice. Methods We developed and validated a mouse strain with an adult-inducible cardiac-specific deletion of AMPKα2, the major cardiac isoform, using the Cre-Lox system (40mg/kg tamoxifen injection on two consecutive days at adult age). At four months after the deletion, cardiac contractility, morphology and metabolism were studied in control and KO mice from both sexes. Results We observed only in male KO mice a decrease of left ventricular ejection fraction (−10%), an increase of the total fibrosis (+64%) and defects in mitochondrial structures. Male KO mice also showed a reduced (−28%) mitochondrial respiration via complex I associated with a different cardiolipin species distribution. Conclusion Our results reveal in adult healthy hearts, a sex-specificity in the effects of AMPKα2 deletion, leading to impaired contractile function related to metabolic and non-metabolic alterations only in male mice.


Perception ◽  
1995 ◽  
Vol 24 (8) ◽  
pp. 969-973 ◽  
Author(s):  
Edward P Chronicle ◽  
Mei-Yin Chan ◽  
Charlotte Hawkings ◽  
Karen Mason ◽  
Kathryn Smethurst ◽  
...  

Measurements taken from the nose are among the most important physical variables which discriminate statistically between male and female faces, yet several investigators have claimed that it is difficult to judge sex on the basis of noses presented in isolation. Previous work on the isolated nose has, however, involved the use of frontal views only, which may have obscured important physical differences between the noses of males and females. An investigation of the accuracy of judgments of the sex of isolated noses observed in frontal, profile, and three-quarter views by male and female subjects is reported. Judgment of sex was performed significantly more accurately than chance in all cases except for frontal views of female noses, where judgment was significantly less accurate than chance. Analysis of variance demonstrated a significant interaction of sex of nose and view of nose, such that male noses were identified better in frontal and in profile views, but female noses better in the three-quarter view. It is suggested that one possible reason for the seemingly contradictory role of the nose in previous studies of sex judgment is that all noses look more male in frontal views. For a nose to be perceived as female, its distinctive shape must be made available to the perceiver; this is most likely from the three-quarter view.


1988 ◽  
Vol 254 (2) ◽  
pp. 367-372 ◽  
Author(s):  
Y Murakami ◽  
M Marumo ◽  
S I Hayashi

Antizyme, a protein inhibitor of ornithine decarboxylase (ODC), was shown to be induced in mouse kidney by repeated injection of putrescine. Antizyme was also present as a complex with ODC in the kidney of untreated mouse. The amount of the renal ODC-antizyme complex was 3-fold higher in male mice than in female mice. On the contrary, the proportion of ODC present as a complex with antizyme was 24-fold higher in females than in males, and the decay of renal ODC activity after cycloheximide treatment was about 5-fold more rapid in females than in males. Administration of testosterone to female mice, a procedure known to prolong the half-life of renal ODC, increased both ODC activity and the content of ODC-antizyme complex, but decreased the antizyme/ODC ratio in the kidney. These results are consistent with the previous observation in HTC cells that the decay rate of ODC activity in the presence of cycloheximide correlated well with the proportion of ODC present as a complex with antizyme, suggesting the ubiquitous role of antizyme in ODC degradation.


Sign in / Sign up

Export Citation Format

Share Document