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1.
The objective of this work was to evaluate the associations between levels of endogenous sex hormones in women at midlife and lipoprotein subclasses. One hundred and twenty women (68 late peri-/postmenopausal and 52 pre-/early perimenopausal) from the Study of Women’s Health Across the Nation (Pittsburgh site) were included. Lipoprotein subclasses were quantified using NMR spectroscopy. Participants (57.5% White and 42.5% Black) were 50.4 ± 1.9 years old. Adjusting for age, race, cycle day of blood draw, BMI, physical activity, and alcohol consumption, a negative correlation was found between estradiol (E2) and medium-small LDL particle (LDL-P) concentration (ρ = −0.19, P = 0.04). Further, E2 was positively correlated with HDL particle (HDL-P) size (ρ = 0.22, P = 0.02). For sex hormone binding globulin (SHBG), independent negative correlation was found with total small LDL-P concentration. SHBG was also positively correlated with LDL-P and HDL-P sizes (P < 0.05 for all). For free androgen index (FAI), positive correlations were found with concentrations of total VLDL particles, total LDL-Ps, and total small LDL-Ps. Additionally, FAI was negatively correlated with large HDL-P concentration, and HDL-P and LDL-P sizes (P < 0.05 for all). Lower levels of E2 and SHBG, and higher levels of FAI were associated with a more atherogenic profile of lipoprotein subclasses. Sex hormone levels at midlife may increase women’s risk of coronary heart disease.  相似文献   

2.
Dysregulation of hypothalamic–pituitary–adrenal (HPA) axis activation is associated with changes in addiction‐related behaviors. In this study, we tested whether sex differences in the acute effects of methamphetamine (MA) exposure involve differential activation of the HPA axis. Male and female mice were injected with MA (1 mg/kg) or saline for comparison of plasma corticosterone and analysis of the immediate early gene c‐Fos in brain. There was a prolonged elevation in corticosterone levels in female compared to male mice. C‐Fos was elevated in both sexes following MA in HPA axis‐associated regions, including the hypothalamic paraventricular nucleus (PVN), central amygdala, cingulate, and CA3 hippocampal region. MA increased the number of c‐Fos and c‐Fos/glucocorticoid receptor (GR) dual‐labeled cells to a greater extent in males than females in the cingulate and CA3 regions. MA also increased the number of c‐fos/vasopressin dual‐labeled cells in the PVN as well as the number and percentage of c‐Fos/GR dual‐labeled cells in the PVN and central amygdala, although no sex differences in dual labeling were found in these regions. Thus, sex differences in MA‐induced plasma corticosterone levels and activation of distinct brain regions and proteins involved in HPA axis regulation may contribute to sex differences in acute effects of MA on the brain.

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3.
Throughout the second and third trimesters, the human placenta (and the placenta in other anthropoid primates) produces substantial quantities of corticotropin-releasing hormone (placental CRH), most of which is secreted into the maternal bloodstream. During pregnancy, CRH concentrations rise over 1000-fold. The advantages that led selection to favour placental CRH production and secretion are not yet fully understood. Placental CRH stimulates the production of maternal adrenocorticotropin hormone (ACTH) and cortisol, leading to substantial increases in maternal serum cortisol levels during the third trimester. These effects are puzzling in light of widespread theory that cortisol has harmful effects on the fetus. The maternal hypothalamic-pituitary-adrenal (HPA) axis becomes less sensitive to cortisol during pregnancy, purportedly to protect the fetus from cortisol exposure. Researchers, then, have often looked for beneficial effects of placental CRH that involve receptors outside the HPA system, such as the uterine myometrium (e.g. the placental clock hypothesis). An alternative view is proposed here: the beneficial effect of placental CRH to the fetus lies in the fact that it does stimulate the production of cortisol, which, in turn, leads to greater concentrations of glucose in the maternal bloodstream available for fetal consumption. In this view, maternal HPA insensitivity to placental CRH likely reflects counter-adaptation, as the optimal rate of cortisol production for the fetus exceeds that for the mother. Evidence pertaining to this proposal is reviewed.  相似文献   

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Determining whether a stressful event will lead to stress‐resilience or vulnerability depends probably on an adjustable stress response set point, which is most likely effective during postnatal sensory development and involves the regulation of corticotrophin‐releasing hormone (CRH) expression. During the critical period of thermal‐control establishment in 3‐day‐old chicks, heat stress was found to render resilient or sensitized response, depending on the ambient temperature. These two different responses were correlated with the amount of activation of the hypothalamic–pituitary–adrenal (HPA) axis. The expression of CRH mRNA in the hypothalamic paraventricular nucleus was augmented during heat challenge a week after heat conditioning in chicks which were trained to be vulnerable to heat, while it declined in chicks that were trained to be resilient. To study the role of CRH in HPA‐axis plasticity, CRH or Crh‐antisense were intracranially injected into the third ventricle. CRH caused an elevation of both body temperature and plasma corticosterone level, while Crh‐antisense caused an opposite response. Moreover, these effects had long term implications by reversing a week later, heat resilience into vulnerability and vice versa. Chicks that had been injected with CRH followed by exposure to mild heat stress, normally inducing resilience, demonstrated, a week later, an elevation in body temperature, and Crh mRNA level similar to heat vulnerability, while Crh‐antisense injected chicks, which were exposed to harsh temperature, responded in heat resilience. These results demonstrate a potential role for CRH in determining the stress resilience/vulnerability balance. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 842–853, 2015  相似文献   

6.
Objective: The objective was to evaluate ghrelin and growth hormone (GH) interactions and responses to a growth hormone‐releasing hormone (GHRH)/arginine test in severe obesity before and after surgically‐induced weight loss. Research Methods and Procedures: Our study population included 11 severely obese women 39 ± 12 years of age, with a mean BMI of 48.6 ± 2.4 kg/m2, re‐studied in a phase of stabilized body weight, with a BMI of 33.4 ± 1.2 kg/m2, 18 months after having successfully undergone biliopancreatic diversion (BPD). A GHRH/arginine test was performed before and 18 months after BPD to evaluate ghrelin and GH interactions. Active ghrelin, measured by radioimmunoassay (RIA), and GH, measured by chemiluminescence assay, were assayed before and after the GHRH/arginine test. Results: Fasting serum GH levels and GH area under the curve (AUC) significantly increased from 0.2 ± 0.05 ng/mL to 1 ± 0.3 ng/mL (p < 0.05) and from 514.76 ± 98.7 ng/mL for 120 minutes to 1957.3 ± 665.1 ng/mL for 120 minutes after bariatric surgery (p < 0.05), respectively. Although no significant change in fasting ghrelin levels was observed (573 ± 77.9 before BPD vs. 574.1 ± 32.7 after BPD), ghrelin AUC significantly increased from ?3253.9 ± 2180.9 pg/mL for 120 minutes to 1142.3 ± 916.4 pg/mL for 120 minutes after BPD (p < 0.05). Fasting serum insulin‐like growth factor (IGF)‐1 concentration did not change significantly (133.6 ± 9.9 ng/mL before vs. 153.3 ± 25.2 ng/mL after BPD). Discussion: Our study demonstrates that the mechanisms involved in ghrelin and GH secretion after the secretagogue stimulus (GHRH/arginine) are consistent with patterns observed in other populations.  相似文献   

7.
Groups of sexually undifferentiated sea bass Dicentrarchus labrax were fed with the androgen 17α-methyltestosterone (MT) during sex differentiation. MT treatment increased males from 79±3% in the controls (the usual 3:1 male:female sex ratio of cultured sea bass) to 100±0%, implying that in the treated groups one out of each five resulting males was a masculinized female (neomale). Thirteen males from the MT treated groups were taken as the parental generation and their sperm used to individually fertilize a pool of eggs from unrelated females. The probability of having at least one neomale was 95% and most probably two or three of the males used were neomales. The offspring from each family were reared separately under the same environmental conditions. Samples were taken at 11 and 15 months of age, during and after sex differentiation, respectively. Results showed that females predominated among the larger fish whereas males and undifferentiated fish predominated among the smaller ones. Intersexes exhibited an intermediate size. All fish with a body length smaller than 12 cm were undifferentiated. These results suggest that sex differentiation is more dependent on length than on age. At 15 months, sex ratios were male-biased in all families, except one (females ranged from 5 to 50%) and only two families had sex ratios not significantly different from 1:1, suggesting that the mechanism of sex determination in the sea bass is not of a XX/XY or ZW/ZZ type since no family exhibited a female-biased progeny, as would be expected from both types. Results support the hypothesis that factors other than genetic, i.e., environmental, may act epigenetically on the sex determination mechanisms of sea bass, as has been demonstrated in other fishes.  相似文献   

8.
We recently showed that a genetic polymorphism (rs878886) in the human corticotropin‐releasing hormone receptor 1 (CRHR1) is associated with reduced fear‐conditioned responses to a threat cue. This is a potentially important finding considering that the failure to acquire fear contingencies can leave an individual in a maladaptive state of more generalized anxiety. Consistent with that idea, the CRHR1‐dependent fear acquisition deficit translated into heightened contextual anxiety when taking genetic variability within the serotonin transporter long polymorphic region (5‐HTTLPR) into account. To replicate our previous findings, we conducted a replication study in 224 healthy medication‐free human subjects using the exact same cue and context virtual reality fear‐conditioning procedure as in study by Heitland et al. (2013). In the replication study, consistent with the original findings, CRHR1 rs878886 G‐allele carriers showed reduced acquisition of cue‐specific fear‐conditioned responses compared with C/C homozygotes. Also, in this larger sample the cue acquisition deficit of G‐allele carriers translated into heightened contextual anxiety, even independent of 5‐HTT gene variation. In contrast to our earlier findings, there was an additional interaction effect of CRHR1 rs878886 and the triallelic 5‐HTTLPR/rs25531 variant on cued fear acquisition. In summary, this study replicated the initially reported association of the CRHR1 rs878886 G‐allele with cued fear acquisition deficits, albeit with a different pattern of results regarding the interaction with 5‐HTT variation. This further supports the notion that the human corticotropin‐releasing hormone plays a role in the acquisition of fears.  相似文献   

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Given sex‐related differences in brain disorders, it is of interest to study if there is a sex difference in the permeability of the blood‐cerebrospinal fluid barrier (BCSFB) and the blood‐brain barrier (BBB). The CSF/serum albumin ratio (QAlb) is a standardized biomarker that evaluates the function of these barriers. In previous studies, contradictory results have been reported with respect to sex difference using this quotient, possibly because of small population sizes and heterogeneity with respect to ages. QAlb measurements in more than 20 000 patients between 1 and 90 years visiting our hospitals revealed a significant sex difference in all age groups also when excluding patients with pathologically high CSF albumin > 400 mg/L. Similar pattern was found in 335 healthy volunteers in similar age intervals. Although also other factors are likely important, our observation is consistent with lower integrity of the brain barriers in males. If the difference in QAlb is caused mainly by a difference in barrier function, this may require different drug doses and strategies for efficient central nervous system (CNS) delivery in males and females, as well as it may indicate differences in brain metabolism. Moreover, our study emphasizes that different reference values should be used both for different ages and sexes.  相似文献   

12.
Using the Xiphophorus fish melanoma model, we show a strong male bias for sunlight‐induced malignant melanoma, consistent with that seen in the human population. To examine underlying factors, we exposed adult X. couchianus fish to a single, sublethal dose of UVB and measured circulating sex steroid hormones and expression of associated hormone receptor genes over a 24‐h period. We found that a single exposure had profound effects on circulating levels of steroid hormones with significant decreases for all free sex steroids at 6 and 24 h and increases in conjugated 2‐estradiol and 11‐ketotestosterone at 6 and 24 h, respectively. Whereas ARα expression increased in male and female skin, neither ARβ nor either of the ERs showed significant responses to UVB in either sex. The rapid response of male androgens and their receptors in the skin after UVB irradiation implicates hormones in the male bias of skin cancer and suggests that the photoendocrine response immediately after UV exposure may be relevant to melanomagenesis.  相似文献   

13.
There are few papers about physiological indices in Callithrix penicillata, an increasing primate model in biomedicine. We investigated levels of plasmatic cortisol, plasmatic glucose, free fatty acids, blood cells, tympanic temperature, rectal temperature in C. penicllata, under a fast restraint. Measures of body and weight were accomplished. Males and females were not different regarding any measurements. Body measurements indicated differences between adults and juveniles. Adults showed higher hematocrit and a tendency for higher free fatty acids than juveniles. Right tympanic temperature was higher in adults than juveniles. This result suggests a higher reaction metabolism in adults than juveniles under a restraint stress. Due to the short-time of collecting the data, plasmatic cortisol did not influence physiological parameters. Therefore, we suggest that present results could be considered referential values of C. penicillata physiology.  相似文献   

14.
Sex ratio biases are often inconsistent, both among and within species and populations. While some of these inconsistencies may be due to experimental design, much of the variation remains inexplicable. Recent research suggests that an exclusive focus on mothers may account for some of the inconsistency, with an increasing number of studies showing variation in sperm sex ratios and seminal fluids. Using fluorescent in‐situ hybridization, we show a significant population‐level Y‐chromosome bias in the spermatozoa of wild tammar wallabies, but with significant intraindividual variation between males. We also show a population‐level birth sex ratio trend in the same direction toward male offspring, but a weaning sex ratio that is significantly female‐biased, indicating that males are disproportionately lost during lactation. We hypothesize that sexual conflict between parents may cause mothers to adjust offspring sex ratios after birth, through abandonment of male pouch young and reactivation of diapaused embryos. Further research is required in a captive, controlled setting to understand what is driving and mechanistically controlling sperm sex ratio and offspring sex ratio biases and to understand the sexually antagonistic relationship between mothers and fathers over offspring sex. These results extend beyond sex allocation, as they question studies of population processes that assume equal input of sex chromosomes from fathers, and will also assist with future reproduction studies for management and conservation of marsupials.  相似文献   

15.
Mammalian skin incorporates a local equivalent of the hypothalamic–pituitary–adrenal (HPA) axis that is critical in coordinating homeostatic responses against external noxious stimuli. Ultraviolet radiation B (UVB) is a skin-specific stressor that can activate this cutaneous HPA axis. Since C57BL/6 (B6) and DBA/2J (D2) strains of mice have different predispositions to sensorineural pathway activation, we quantified expression of HPA axis components at the gene and protein levels in skin incubated ex vivo after UVB or sham irradiation. Urocortin mRNA was up-regulated after all doses of UVB with a maximum level at 50 mJ/cm2 after 12 h for D2 and at 200 mJ/cm2 after 24 h for B6. Proopiomelanocortin mRNA was enhanced after 6 h with the peak after 12 h and at 200 mJ/cm2 for both genotypes of mice. ACTH levels in tissue and media increased after 24 h in B6 but not in D2. UVB stimulated β-endorphin expression was higher in D2 than in B6. Melanocortin receptor 2 mRNA was stimulated by UVB in a dose-dependent manner, with a peak at 200 mJ/cm2 after 12 h for both strains. The expression of Cyp11a1 mRNA — a key mitochondrial P450 enzyme in steroidogenesis, was stimulated at all doses of UVB irradiation, with the most pronounced effect after 12–24 h. UVB radiation caused, independently of genotype, a dose-dependent increase in corticosterone production in the skin, mainly after 24 h of histoculture. Thus, basal and UVB stimulated expression of the cutaneous HPA axis differs as a function of genotype: D2 responds to UVB earlier and with higher amplitude than B6, while B6 shows prolonged (up to 48 h) stress response to a noxious stimulus such as UVB.  相似文献   

16.
为探索黄花倒水莲春梢生理生化特性的差异以及不同内源激素的变化规律,该文对黄花倒水莲春梢的生长动态进行监测,采用间接酶联免疫吸附法(ELISA)测定脱落酸(ABA)、生长素(IAA)、赤霉素(GA)、乙烯(ETH)和玉米素核苷(ZR)五种内源激素含量的动态变化,并对两者间的相关性进行分析。结果表明:(1)黄花倒水莲春梢生长发育过程可分为快速增长期(0~12 d)、生长转折期(16~20 d)和缓慢增长期(24~32 d)三个阶段。(2)内源激素ABA、GA、ETH和ZR含量在缓慢增长期显著高于快速增长期和生长转折期,IAA含量各时期差异较小。(3)春梢长、底部叶长和叶宽在快速增长期与ABA、GA、ETH和ZR含量呈负相关,且与ZR含量具有一定显著性,与IAA含量呈正相关;生长转折期,各指标与GA、ETH和ZR含量呈正相关,与GA含量具有一定显著性,与ABA含量呈负相关;缓慢增长期,各指标与五种内源激素含量均呈正相关,与IAA和ZR含量具有一定显著性。该研究结果为生产上利用外源激素调控黄花倒水莲春梢抽出以及生长提供了理论基础。  相似文献   

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Bonobos are known for their pacifistic behavior and their large repertoire of behaviors that are thought to serve conflict resolution. One is an unusual form of ventro‐ventral mounting that facilitates genital contacts (GC). Various hypotheses have been proposed to explain its function. In this study we tested predictions of the tension regulation hypothesis using salivary cortisol as a marker for social stress. The results indicate a temporal relationship between GC and cortisol levels. Compared with baseline data and matched samples of unrestricted food access, rates of GC increased when access to food sources was restricted. Cortisol levels were highest when access to food was constrained. However, because the behavioral and hormonal responses occurred when viewing the stimulus at a distance and preceded the physical presence of the stimulus, we conclude that the anticipation of a competitive situation was sufficient to induce social stress. Contrary to our prediction, targets of aggression did not have higher rates of GC nor did they solicit GC more often than others. Furthermore, higher GC rates did not correlate with a more pronounced decrease in cortisol levels. Not all results obtained in this study supported the predictions concerning the regulatory function of GC on social tension and further research is needed to explore this question. However, the results indicate that the anticipation of competition may be sufficient to induce a costly physiological response, and that high levels of resource competition may have lasting effects on physical stress and stress management. Am. J. Primatol. 71:223–232, 2009. © 2008 Wiley‐Liss, Inc.  相似文献   

19.
Objective: Understanding factors influencing bone mineral accrual is critical to optimize peak bone mass during childhood. The epidemic of pediatric obesity and reported higher incident of fracture risk in obese children led us to study the influence of fat mass on bone mineral content (BMC) in children. Research Methods and Procedures: Height; weight; pubertal stage; and BMC, non‐bone fat‐free mass (nbFFM), and fat mass (FM) by DXA were obtained in a multiethnic group of healthy children (444 girls/482 boys; 6 to 18 years old) recruited in the New York metropolitan area. Regression techniques were used to explore the relationship between BMC and FM, with age, height, nbFFM, pubertal stage, sex, and ethnicity as covariates. Results: Because there were significant sex interactions, separate regression analyses were performed for girls and boys. Although ln(nbFFM) was the greatest predictor of ln(BMC), ln(FM) was also a significant predictor in prepubertal boys and all girls but not in pubertal boys. This effect was independent of ethnicity. Discussion: FM was a determinant of BMC in all girls but in only prepubertal boys. Our study confirms nbFFM as the greatest predictor of BMC but is the first to find a sex difference in the effect of puberty on the relationship of FM to BMC. Our results suggest that, in two individuals of the same sex and weight, the one with greater fat mass will have lower BMC, especially pubertal boys. The implications of these findings for achievement of optimal peak bone mass in a pediatric population with an unprecedented incidence of overweight and “overfat” status remain to be seen.  相似文献   

20.

Background

High urine volume enhances urinary free cortisol (UFF) and cortisone (UFE) excretion rates in normal-weight adults and children. Renal excretion rates of glucocorticoids (GC) and their metabolites are frequently altered in obesity. The aim of the present study was to investigate whether UFF and UFE excretion is also affected by urine volume in severely obese subjects.

Experimental

In 24-h urine samples of 59 extremely obese subjects (mean BMI 45.3 ± 8.9 kg/m2) and 20 healthy lean subjects (BMI 22.1 ± 1.8 kg/m2), UFF and UFE, tetrahydrocortisol (THF), 5α-tetrahydrocortisol (5α-THF), and tetrahydrocortisone (THE) were quantified by RIA. The sum of THF, 5α-THF, and THE (GC3), the three major GC metabolites, reflects daily cortisol secretion. 11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity was assessed by the ratio UFE/UFF. Daily GC excretion rates were corrected for urine creatinine and adjusted for gender and body weight.

Results

In extremely obese subjects, urine volume was significantly associated with creatinine-corrected UFE and 11β-HSD2 activity after adjustment for gender and BMI (r = 0.47, p = 0.0002 and r = 0.31, p = 0.02, respectively). However, urine volume was not associated with creatinine-corrected UFF and GC3 (p = 0.4 and p = 0.6, respectively). In lean controls, urine volume was significantly associated with creatinine-corrected UFE and UFF (r = 0.58, p = 0.01 and r = 0.55, p = 0.02, respectively), whereas urine volume was not associated with 11β-HSD2 activity after appropriate adjustment (p = 0.3).

Conclusions

In severe obesity, in contrast to normal weight, renal excretion of UFE, but not of UFF is affected by fluid intake. This discrepancy may be due to the increased renal 11β-HSD2 activity in obesity.  相似文献   

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