Androgen receptor gene polymorphism and sex hormones in elderly men: the Tromso study.
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ABSTRACT:
SUBMITTER: Skjaerpe PA
PROVIDER: S-EPMC3735021 | biostudies-other | 2009 Mar
REPOSITORIES: biostudies-other
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Project description:Androgen receptor genes (AR) have been found to have associations with reproductive development, behavioral traits, and disorders in humans. However, the influence of similar genetic effects on the behavior of other animals is scarce. We examined the loci AR glutamine repeat (ARQ) in 44 Grevy's zebras, 23 plains zebras, and three mountain zebras, and compared them with those of domesticated horses. We observed polymorphism among zebra species and between zebra and horse. As androgens such as testosterone influence aggressiveness, AR polymorphism among equid species may be associated with differences in levels of aggression and tameness. Our findings indicate that it would be useful to conduct further studies focusing on the potential association between AR and personality traits, and to understand domestication of equid species.
| S-EPMC4501558 | biostudies-literature
Project description:ContextAs men age, the prevalence of frailty increases whereas levels of androgens decline. Little is known about the relation between these factors.ObjectiveThe aim of this study was to assess cross-sectional and longitudinal associations of estradiol, bioavailable estradiol, testosterone, bioavailable testosterone (bioT), and SHBG with frailty status.Design and settingThe Osteoporotic Fractures in Men (MrOS) study was conducted at six U.S. clinical centers.ParticipantsA total of 1469 community-dwelling men at least 65 yr old with baseline data participated; 1245 men had frailty status reassessed 4.1 yr later.Main outcome measureProportional odds models estimated the likelihood of greater frailty status. Frail men had at least three of the following: weakness, slowness, low activity, exhaustion, and shrinking/sarcopenia; intermediate men had one or two criteria; and robust men had none. At follow-up, death was included as an additional ordinal outcome. Sex hormones were assayed by spectrometry/chromatographic methods.ResultsIn cross-sectional analyses, men in the lowest quartile of bioT had 1.39-fold (95% confidence interval, 1.02, 1.91) increased odds of greater frailty status compared to men in the highest quartile after adjustment for covariates including age, body size, health status, and medical conditions. In age-adjusted longitudinal analyses, men in the lowest quartile of bioT had 1.51-fold (95% confidence interval, 1.10, 2.07) increased odds of greater frailty status 4.1 yr later. This association was largely attenuated by adjustment for covariates. No other hormones were associated in a cross-sectional or longitudinal manner with frailty status after adjustment.ConclusionsLow levels of bioT were independently associated with worse baseline frailty status. Frailty status should be considered as an outcome in trials of testosterone supplementation.
| S-EPMC2758722 | biostudies-literature
Project description:Women are at a 2-fold risk of developing late-onset Alzheimer's disease (AD) (onset at 65 years of age or older) compared with men. During perimenopausal years, women undergo hormonal changes that are accompanied by metabolic, cardiovascular, and inflammatory changes. These all together have been suggested as risk factors for late-onset AD. However, not all perimenopausal women develop AD; we hypothesize that certain genetic factors might underlie the increased susceptibility for developing AD in postmenopausal women. We investigated the Androgen Receptor gene (AR) in a clinical cohort of male and female AD patients and normal control subjects by sequencing all coding exons and evaluating the length and distribution of the CAG repeat in exon 1. We could not establish a correlation between the repeat length, sex, and the disease status, nor did we identify possible pathogenic variants. AR is located on the X chromosome; to assess its role in AD, X-inactivation patterns will need to be studied to directly correlate the actual expressed repeat length to a possible sex-specific phenotypic effect.
| S-EPMC4012749 | biostudies-literature
Project description:The association between sex hormones and sex hormone binding globin (SHBG) with vertebral fractures in men is not well studied. In these analyses, we determined whether sex hormones and SHBG were associated with greater likelihood of vertebral fractures in a prospective cohort study of community dwelling older men. We included data from participants in MrOS who had been randomly selected for hormone measurement (N=1463, including 1054 with follow-up data 4.6years later). Major outcomes included prevalent vertebral fracture (semi-quantitative grade≥2, N=140, 9.6%) and new or worsening vertebral fracture (change in SQ grade≥1, N=55, 5.2%). Odds ratios per SD decrease in sex hormones and per SD increase in SHBG were estimated with logistic regression adjusted for potentially confounding factors, including age, bone mineral density, and other sex hormones. Higher SHBG was associated with a greater likelihood of prevalent vertebral fractures (OR: 1.38 per SD increase, 95% CI: 1.11, 1.72). Total estradiol analyzed as a continuous variable was not associated with prevalent vertebral fractures (OR per SD decrease: 0.86, 95% CI: 0.68 to 1.10). Men with total estradiol values ≤17pg/ml had a borderline higher likelihood of prevalent fracture than men with higher values (OR: 1.46, 95% CI: 0.99, 2.16). There was no association between total testosterone and prevalent fracture. In longitudinal analyses, SHBG (OR: 1.42 per SD increase, 95% CI: 1.03, 1.95) was associated with new or worsening vertebral fracture, but there was no association with total estradiol or total testosterone. In conclusion, higher SHBG (but not testosterone or estradiol) is an independent risk factor for vertebral fractures in older men.
| S-EPMC4755786 | biostudies-literature
Project description:Many women with hyperandrogenemia suffer from irregular menses and infertility. However, it is unknown whether androgens directly affect reproduction. Since animal models of hyperandrogenemia-induced infertility are associated with obesity, which may impact reproductive function, we have created a lean mouse model of elevated androgen using implantation of low dose dihydrotestosterone (DHT) pellets to separate the effects of elevated androgen from obesity. The hypothalamic-pituitary-gonadal axis controls reproduction. While we have demonstrated that androgen impairs ovarian function, androgen could also disrupt neuroendocrine function at the level of brain and/or pituitary to cause infertility. To understand how elevated androgens might act on pituitary gonadotropes to influence reproductive function, female mice with disruption of the androgen receptor (Ar) gene specifically in pituitary gonadotropes (PitARKO) were produced. DHT treated control mice with intact pituitary Ar (Con-DHT) exhibit disrupted estrous cyclicity and fertility with reduced pituitary responsiveness to GnRH at the level of both calcium signaling and LH secretion. These effects were ameliorated in DHT treated PitARKO mice. Calcium signaling controls GnRH regulation of LH vesicle exotocysis. Our data implicated upregulation of GEM (a voltage-dependent calcium channel inhibitor) in the pituitary as a potential mechanism for androgen's pathological effects. These results demonstrate that gonadotrope AR, as an extra-ovarian regulator, plays an important role in reproductive pathophysiology.
| S-EPMC6777920 | biostudies-literature
Project description:BACKGROUND:Endogenous sex hormones have been related to cardiovascular outcomes and mortality. We hypothesized that sex hormones are related to atrial fibrillation (AF) in a community-based cohort of middle-aged to older men. METHODS AND RESULTS:We examined testosterone, estradiol, and dehydroepiandrosterone sulfate in relation to incident AF in men participating in the Framingham Heart Study. We assessed the 10-year risk of AF in multivariable-adjusted hazard models. The cohort consisted of 1251 men (age, 68.0±8.2 years), of whom 275 developed incident AF. We identified a significant interaction between age and testosterone and, therefore, stratified men into age 55 to 69 years (n=786), 70 to 79 years (n=351), and ?80 years (n=114). In men aged 55 to 69 years, each 1 SD decrease in testosterone was associated with hazard ratio (HR) 1.30 (95% confidence interval [CI], 1.07-1.59) for incident AF. The association between testosterone and 10-year incident AF in men 70 to 79 years did not reach statistical significance. In men?80 years, a 1 SD decrease in testosterone was associated with HR 3.53 (95% CI, 1.96-6.37) for AF risk. Estradiol was associated with incident AF (HR, 1.12; 95% CI, 1.01-1.26). Dehydroepiandrosterone sulfate had a borderline association with risk of AF that was not statistically significant (HR, 1.12; 95% CI, 0.99-1.28). CONCLUSIONS:Testosterone and estradiol are associated with incident AF in a cohort of older men. Testosterone deficiency in men?80 years is strongly associated with AF risk. The clinical and electrophysiological mechanisms underlying the associations between sex hormones and AF in older men merit continued investigation.
| S-EPMC4035016 | biostudies-literature
Project description:BackgroundPlatelet-derived growth factor (PDGF) D has been reported to be active in fibroblasts, and in areas of myocardial infarction. In this longitudinal study we evaluated the association between PDGF-D polymorphism and cardiovascular mortality, and attempted to discover whether specific genotype differences regarding risk could be observed, and if gender differences could be seen.MethodsFour hundred seventy-six elderly community participants were included in this study. All participants underwent a clinical examination, echocardiography, and blood sampling including PDGF-D single nucleotide polymorphism (SNP) analyses of the rs974819 A/A, G/A and G/G SNP. The follow-up time was 6.7 years.ResultsNo specific genotype of rs974819 demonstrated increased cardiovascular mortality in the total population, however, the male group with genotypes A/A and G/A demonstrated an increased risk that persisted in a multivariate evaluation where adjustments were made for well-known cardiovascular risk factors (2.7 fold compared with the G/G genotype). No corresponding finding was observed in the female group.ConclusionWe report here for the first time that the genotypes G/A or A/A of the SNP rs974819 near PDGF-D exhibited a 2.7 fold increased cardiovascular mortality risk in males. Corresponding increased risk could not be observed in either the total population and thus not in the female group. However, the sample size is was small and the results should be regarded as hypothesis-generating, and thus more research in the field is recommended.
| S-EPMC5009508 | biostudies-literature
Project description:IntroductionSeveral findings suggest that testosterone (T) is neuroprotective and that declining T levels during aging are associated with cognitive and brain pathologies; however, little is known on T and brain health in middle-age. We examined the relationships of total T, bioavailable T, and sex hormone binding globulin (SHBG) levels with total and regional gray matter (GM) and white matter (WM) volumes in middle-aged men. We also evaluated the association of sex hormone levels with cognitive function.MethodsAnalysis included 267 community-dwelling men participating in the Coronary Artery Risk Development in Young Adults (CARDIA) brain magnetic resonance imaging (MRI) substudy. Total T, bioavailable T, and SHBG levels were measured at three times from the 2nd to 4th decade of life; brain volumes were measured at the ages of 42-56. Associations were estimated using linear regression models, adjusted for several potential confounders.ResultsHigher SHBG levels were associated with greater total WM volume (+3.15 cm3 [95% confidence interval [CI] = 0.01, 6.28] per one standard deviation higher SHBG). Higher SHBG levels were associated with lower total and regional GM volumes overall and significantly with smaller parietal GM volume (-0.96 cm3 [95%CI = -1.71, -0.21]). T levels were not related to brain volumes. Neither T nor SHBG levels were associated with cognitive function.ConclusionResults suggest a role for SHBG in structural brain outcomes in men and emphasize the value of investigating SHBG levels as modulators of sex hormone and metabolic pathways regulating brain and behavioral characteristics in men.
| S-EPMC5651379 | biostudies-literature
Project description:The androgen receptor (AR) gene polymorphism in humans is linked to aggression and may also be linked to reproduction. Here we report associations between AR gene polymorphism and aggression and reproduction in two small-scale societies in northern Tanzania (Africa)--the Hadza (monogamous foragers) and the Datoga (polygynous pastoralists). We secured self-reports of aggression and assessed genetic polymorphism of the number of CAG repeats for the AR gene for 210 Hadza men and 229 Datoga men (aged 17-70 years). We conducted structural equation modeling to identify links between AR gene polymorphism, aggression, and number of children born, and included age and ethnicity as covariates. Fewer AR CAG repeats predicted greater aggression, and Datoga men reported more aggression than did Hadza men. In addition, aggression mediated the identified negative relationship between CAG repeats and number of children born.
| S-EPMC4546275 | biostudies-literature
Project description:Although previous studies have suggested a potential role of sex hormones in the etiology of colorectal cancer (CRC), no study has yet examined the associations between circulating sex hormones and survival among CRC patients. We prospectively assessed the associations of prediagnostic plasma concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone and sex hormone-binding globulin (SHBG) with CRC-specific and overall mortality among 609 CRC patients (370 men and 239 postmenopausal women not taking hormone therapy at blood collection) from four U.S. cohorts. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard regression. We identified 174 deaths (83 CRC-specific deaths) in men and 106 deaths (70 CRC-specific deaths) in women. In men, higher circulating level of free testosterone was associated with lower risk of overall (the highest vs. lowest tertiles, HR = 0.66, 95% CI, 0.45-0.99, ptrend = 0.04) and possibly CRC-specific mortality (HR = 0.73, 95% CI, 0.41-1.29, ptrend = 0.27). We generally observed nonsignificant inverse associations for other sex steroids, and a positive association for SHBG with CRC-specific mortality among male patients. In women, however, we found a suggestive positive association of estrone with overall (HR = 1.54, 95% CI, 0.92-2.60, ptrend = 0.11) and CRC-specific mortality (HR = 1.96, 95% CI, 1.01-3.84, ptrend = 0.06). Total estradiol, free estradiol and free testosterone were generally suggestively associated with higher risk of mortality among female patients, although not statistically significant. These findings implicated a potential role of endogenous sex hormones in CRC prognosis, which warrant further investigation.
| S-EPMC7895324 | biostudies-literature