Sex differences in the effects of amiloride on formalin test nociception in mice

2006 ◽  
Vol 291 (2) ◽  
pp. R335-R342 ◽  
Author(s):  
Mona Lisa Chanda ◽  
Jeffrey S. Mogil

Amiloride is a nonspecific blocker of acid-sensing ion channels (ASICs) that have been recently implicated in the mediation of mechanical and chemical/inflammatory nociception. Preliminary data using a transgenic model are suggestive of sex differences in the role of ASICs. We report here that systemic administration of amiloride (10–70 mg/kg ip) produces a robust, dose-dependent blockade of late/tonic phase nociceptive behavior on the mouse formalin test (5%; 20 μl) in female but not male mice, completely abolishing the known sex difference in formalin test response. Adult gonadectomy produced a “switching” of sex differences in amiloride efficacy, with castrated males displaying an amiloride blockade and ovariectomized females rendered less sensitive to amiloride. Gonadectomized mice could be switched back to their intact status using chronic estrogen benzoate or testosterone propionate replacement via osmotic minipump (6 μg/day or 250 μg/day, respectively). It is unclear whether this striking sex difference is due to sex-specific involvement of ASICs in pain processing, but the present data represent one of the first demonstrations of pain-related sex differences with no obvious opioid involvement.

2002 ◽  
Vol 173 (1) ◽  
pp. 113-122 ◽  
Author(s):  
AI Turner ◽  
BJ Canny ◽  
RJ Hobbs ◽  
JD Bond ◽  
IJ Clarke ◽  
...  

There are sex differences in the response to stress and in the influence of stress on reproduction which may be due to gonadal steroids but the nature of these differences and the role of the gonads are not understood. We tested the hypotheses that sex and the presence/absence of gonads (gonadal status) will influence the cortisol response to injection of ACTH, insulin-induced hypoglycaemia and isolation/restraint stress, and that sex and gonadal status will influence the secretion of LH in response to isolation/restraint stress. Four groups of sheep were used in each of three experiments: gonad-intact rams, gonadectomised rams, gonad-intact ewes in the mid-luteal phase of the oestrous cycle and gonadectomised ewes. In Experiment 1 (n=4/group), jugular blood samples were collected every 10 min for 6 h; after 3 h, two animals in each group were injected (i.v.) with ACTH and the remaining two animals were injected (i.v.) with saline. Treatments were reversed 5 days later so that every animal received both treatments. Experiment 2 (n=4/group) used a similar schedule except that insulin was injected (i.v.) instead of ACTH. In Experiment 3 (n=5/group), blood samples were collected every 10 min for 16 h on a control day and again 2 weeks later when, after 8 h of sampling, all sheep were isolated and restrained for 8 h. Plasma cortisol was significantly (P<0.05) elevated following injection of ACTH or insulin and during isolation/restraint stress. There were no significant differences between the sexes in the cortisol response to ACTH. Rams had a greater (P<0.05) cortisol response to insulin-induced hypoglycaemia than ewes while ewes had a greater (P<0.05) cortisol response to isolation/restraint stress than rams. There was no effect of gonadal status on these parameters. Plasma LH was suppressed (P<0.05) in gonadectomised animals during isolation/restraint stress but was not affected in gonad-intact animals, and there were no differences between the sexes. Our results show that the sex that has the greater cortisol response to a stressor depends on the stressor imposed and that these sex differences are likely to be at the level of the hypothalamo-pituitary unit rather than at the adrenal gland. Since there was a sex difference in the cortisol response to isolation/restraint, the lack of a sex difference in the response of LH to this stress suggests that glucocorticoids are unlikely to be a major mediator of the stress-induced suppression of LH secretion.


2020 ◽  
Author(s):  
Erin Sundermann ◽  
Matthew S. Panizzon ◽  
Xu Chen ◽  
Murray Andrews ◽  
Douglas Galasko ◽  
...  

Abstract Women show greater pathological Tau biomarkers than men along the Alzheimer’s disease (AD) continuum, particularly among apolipoprotein ε-E4 (APOE4) carriers; however, the reason for this sex difference in unknown. Sex differences often indicate an underlying role of sex hormones. We examined whether testosterone levels might influence this sex difference and the modifying role of APOE4 status. Analyses included 172 participants (25 cognitively normal, 97 mild cognitive impairment, 50 AD participants) from the Alzheimer’s Disease Neuroimaging Initiative (34% female, 54% APOE4+, aged 55–90). We examined the separate and interactive effects of plasma testosterone levels and APOE4 on cerebrospinal fluid phosphorylated-tau181 (p-Tau) levels in the overall sample, and the sex difference in p-Tau levels before and after adjusting for testosterone. A significant APOE4-by-testosterone interaction revealed that lower testosterone levels related to higher p-Tau levels among APOE4 carriers regardless of sex. As expected, women had higher p-Tau levels than men among APOE4 carriers only, yet this difference was eliminated upon adjustment for testosterone. Results suggest that testosterone is protective against p-Tau particularly among APOE4 carriers. The lower testosterone levels that typically characterize women may predispose them to pathological Tau, particularly among female APOE4 carriers.


2019 ◽  
Vol 39 (9) ◽  
pp. 1133-1146 ◽  
Author(s):  
A Vafa ◽  
SM Afzal ◽  
P Barnwal ◽  
S Rashid ◽  
A Shahid ◽  
...  

Benign prostatic hyperplasia (BPH) is an important key health concern for aging men. Polyphenolic compounds have been found to possess important roles in the inhibition of numerous ailments that involve reactive oxygen species and inflammation. Diosmin is a citrus flavone that possesses antioxidant, anti-inflammatory, antiproliferative, and anticancer activities, so based on these properties of diosmin, we decided to evaluate its effect on testosterone propionate (TP)-induced BPH. A total of 30 Wistar rats were randomly assigned to five groups having six animals in each. This study was of 28 days in which TP (5 mg kg−1) was administered to induce BPH in the last 10 days of the study. It was found that diosmin at the doses of 20 and 40 mg kg−1 significantly reduced malondialdehyde and xanthine oxidase formation in a dose-dependent manner; however, it replenished catalase, glutathione (GSH), and GSH-dependent enzymes, that is, glutathione peroxidase, glutathione reductase, and glutathione- S-transferase significantly against TP-induced BPH. Further, immunohistochemical study showed that diosmin alleviated inflammatory markers (nuclear factor kappa-light-chain-enhancer of activated B cells, cyclooxygenase-2, and interleukin-6). It was also found that diosmin downregulated the expression of androgen receptor and decreased the prostate-specific antigen concentration dose-dependently, significantly against TP-induced BPH. Diosmin also restored histoarchitecture of the prostate in a dose-dependent manner. Findings from the present study revealed the protective role of diosmin against TP-induced BPH in Wistar rats.


1987 ◽  
Vol 21 (4) ◽  
pp. 501-506 ◽  
Author(s):  
A. F. Jorm

The personality trait of neuroticism is thought to be an important risk factor for depression. To ascertain the possible role of neuroticism in producing sex differences in depression, a meta-analysis was carried out on published studies reporting sex- and age-specific norms for neuroticism inventories. A general sex difference was found, with females having higher scores. However, the sex difference was greater in young and middle-aged adults than in children or the very elderly. This age trend in sex differences for neuroticism is similar in form to that previously reported for depression, except that the sex difference for depression completely disappeared in the very young and very old, but the sex difference in neuroticism did not.


1988 ◽  
Vol 117 (3) ◽  
pp. 387-391 ◽  
Author(s):  
A. E. M. Smals ◽  
G. F. F. M. Pieters ◽  
A. G. H. Smals ◽  
P. W. C. Kloppenborg

Abstract. Sellar volume and both basal (r = +0.54, P < 0.02) and GHRH-stimulated (r = +0.41, P < 0.05) GH levels were directly correlated in a group of 28 patients with acromegaly as were the latter indices (r = +0.82, P < 0.001). By subdividing the patients according to sex, a close relation between sellar size and both basal (r = +0.77, P < 0.02) and stimulated GH (r = +0.71, P < 0.02) was found only in the men, not in the women (r = +0.12 and r = +0.02, respectively, P > 0.10). The presence of a tight relation between sellar volume and basal and GHRH stimulated GH levels in male patients with acromegaly and its complete absence in women are equally intriguing and await further elucidation. A modulating role of gonadal steroids in the genesis of this sex differences remain to be assessed.


1973 ◽  
Vol 59 (3) ◽  
pp. 605-621 ◽  
Author(s):  
CARL DENEF ◽  
CAREW MAGNUS ◽  
B. S. McEWEN

SUMMARY The in-vitro conversion of testosterone to 17β-hydroxy-5α-androstan-3-one (5α-dihydrotestosterone, DHT) and 3α, 17β-dihydroxy-5α-androstane (3α-androstanediol, DIOL) in pituitary and slices of brain regions was compared between male and female rats. Intact pituitaries from male rats formed 2·5 times more DHT and 1·5 times more DIOL than those of females. A small sex difference was also detected in the hypothalamus, males again being higher than females. No sex differences could be detected in other brain regions. However, DHT formation in the brain was regionally differentiated with higher conversion rates in hypothalamus than in cortex, hippocampus, amygdala, pineal gland or cerebellum. The highest transformation, however, was found in the mid-brain. Metabolism in the pre-optic area was as low as that in the cortex. 5α-Dihydrotestosterone and DIOL formation in the pituitary increased several-fold after gonadectomy in both sexes and the sex difference disappeared. Little or no increase occurred after thyroidectomy or adrenalectomy. The increase in pituitary DHT formation after gonadectomy could be attenuated or prevented both by treatment with testosterone propionate and with oestradiol benzoate. Replacement therapy, particularly with oestradiol benzoate, gave rise to a sex difference reminiscent of that of normal animals. No significant change in pituitary DHT formation occurred in adult females which had been treated with testosterone propionate on the 4th day of life. The results suggested a close relationship between DHT formation and activity of gonadotrophin secretion, particularly at the level of the pituitary.


2020 ◽  
Author(s):  
Erin Sundermann ◽  
Matthew S. Panizzon ◽  
Xu Chen ◽  
Murray Andrews ◽  
Douglas Galasko ◽  
...  

Abstract Women show greater pathological Tau biomarkers than men along the Alzheimer’s disease (AD) continuum, particularly among apolipoprotein ε-E4 (APOE4) carriers; however, the reason for this sex difference in unknown. Sex differences often indicate an underlying role of sex hormones. We examined whether testosterone levels might influence this sex difference and the modifying role of APOE4 status. Analyses included 172 participants (25 cognitively normal, 97 mild cognitive impairment, 50 AD participants) from the Alzheimer’s Disease Neuroimaging Initiative (34% female, 54% APOE4+, aged 55-90). We examined the separate and interactive effects of plasma testosterone levels and APOE4 on cerebrospinal fluid phosphorylated-tau181 (p-Tau) levels in the overall sample, and the sex difference in p-Tau levels before and after adjusting for testosterone. A significant APOE4-by-testosterone interaction revealed that lower testosterone levels related to higher p-Tau levels among APOE4 carriers regardless of sex. As expected, women had higher p-Tau levels than men among APOE4 carriers only, yet this difference was eliminated upon adjustment for testosterone. Results suggest that testosterone is protective against p-Tau particularly among APOE4 carriers. The lower testosterone levels that typically characterize women may predispose them to pathological Tau, particularly among female APOE4 carriers.


2003 ◽  
Vol 19 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Gisli H. Gudjonsson ◽  
Jon Fridrik Sigurdsson

Summary: The Gudjonsson Compliance Scale (GCS), the COPE Scale, and the Rosenberg Self-Esteem Scale were administered to 212 men and 212 women. Multiple regression of the test scores showed that low self-esteem and denial coping were the best predictors of compliance in both men and women. Significant sex differences emerged on all three scales, with women having lower self-esteem than men, being more compliant, and using different coping strategies when confronted with a stressful situation. The sex difference in compliance was mediated by differences in self-esteem between men and women.


2012 ◽  
Vol 33 (1) ◽  
pp. 35-42 ◽  
Author(s):  
Joseph Glicksohn ◽  
Yamit Hadad

Individual differences in time production should indicate differences in the rate of functioning of an internal clock, assuming the existence of such a clock. And sex differences in time production should reflect a difference in the rate of functioning of that clock between men and women. One way of approaching the data is to compute individual regressions of produced duration (P) on target duration (T), after log transformation, and to derive estimates for the intercept and the slope. One could investigate a sex difference by comparing these estimates for men and women; one could also contrast them by looking at mean log(P). Using such indices, we found a sex difference in time production, female participants having a relatively faster internal clock, making shorter time productions, and having a smaller exponent. The question is whether a sex difference in time production would be found using other methods for analyzing the data: (1) the P/T ratio; (2) an absolute discrepancy (|P-T|) score; and (3) an absolute error (|P-T|/T) score. For the P/T ratio, female participants have a lower mean ratio in comparison to the male participants. In contrast, the |P-T| and |P-T|/T indices seem to be seriously compromised by wide individual differences.


Sign in / Sign up

Export Citation Format

Share Document