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Evidence indicates that master athletes have higher concentration of Sirtuin 1 (Sirt1), lower body fat (BF), and greater activity of the hypothalamic–pituitary–gonadal axis in comparison to untrained peers. However, no published data have demonstrated possible mediation effect of Sirt1 in the interaction of BF and testosterone in this population. Therefore, this study compared and verified possible associations between Sirt1, BF, fat mass index (FMI), testosterone, luteinizing hormone (LH), and testosterone/luteinizing hormone (T/LH) ratio in middle-aged master athletes (n = 54; 51.22 ± 7.76 years) and control middle-aged peers (n = 21; 47.76 ± 8.47 years). Venous blood was collected for testosterone, LH, and Sirt1. BF was assessed through skinfold protocol. Although LH concentration did not differ between groups, master athletes presented higher concentration of Sirt1, testosterone, and T/LH ratio, and lower BF and FMI in relation to age-matched nonathletes. Moreover, Sirt1 correlated positively with testosterone and T/LH ratio, negatively with BF, and was not significantly correlated with LH (mediation analysis revealed the effect of BF on testosterone is mediated by Sirt1 and vice versa; R2 =.1776; p =.032). In conclusion, master athletes have higher testosterone, T/LH ratio, and Sirt1, and lower BF and FMI in relation to untrained peers. Furthermore, Sirt1 was negatively associated with BF and positively associated with testosterone and T/LH ratio. These findings suggest that increased circulating Sirt1, possibly due to the master athlete's training regimens and lifestyle, exhibits a potential mediation effect on the interaction between endocrine function and body composition. [ABSTRACT FROM AUTHOR]

Purpose: We compared the adaptive responses to supramaximal high-intensity interval training (HIIT) individualized according to anaerobic speed reserve (ASR), the 30-15 Intermittent Fitness Test (VIFT), and velocity associated with maximum oxygen uptake (MAS) to determine which approach facilitates more identical adaptations across athletes with different profiles. Methods: Thirty national-level basketball players (age = 28.4 [5] y; body mass = 88.9 [6.3] kg; height = 190 [4.8] cm) were randomly assigned to 3 training groups performing 2 sets of 4, 6, 8, 6, 8, and 10-minute runs (from first to sixth week, respectively), consisting of 15-second running at Δ%20ASR (MAS + 0.2 × ASR), 95%VIFT, and 120%MAS, with 15 seconds recovery between efforts and a 3-minute relief between sets. Results: All 3 interval interventions significantly (P <.05) enhanced maximum oxygen uptake ( V ˙ O 2 max), oxygen pulse ( V ˙ O 2 / HR), first and second ventilatory threshold (VT1 and VT2), cardiac output ( Q ˙ max ), stroke volume, peak and average power output, testosterone levels, and testosterone-to-cortisol ratio following the training period. Different values of interindividual variability (coefficient of variation) for the percentage changes of the measured variables were observed in response to HIITASR, HIITvIFT, and HIITMAS for V ˙ O 2 max (8.7%, 18.8%, 34.6%, respectively), V ˙ O 2 / HR (9.5%, 15.0%, 28.6%), VT1 (9.6%, 19.6%, 34.6%), VT2 (21.8%, 32.4%, 56.7%), Q ˙ max (8.2%, 16.9%, 28.8%), stroke volume (7.9%, 15.2%, 23.5%), peak power output (20%, 22%, 37.3%), average power output (21.1%, 21.3%, 32.5%), testosterone (52.9%, 61.6%, 59.9%), and testosterone-to-cortisol ratio (55.1%, 59.5%, 57.8%). Conclusions: Supramaximal HIIT performed at Δ%20ASR resulted in more uniform physiological adaptations than HIIT interventions prescribed using VIFT or MAS. Although hormonal changes do not follow this approach, all the approaches induced an anabolic effect. [ABSTRACT FROM AUTHOR]

Circadian, infradian, and seasonal changes in steroid hormone secretion have been tied to changes in brain volume in several mammalian species. However, the relationship between circadian changes in steroid hormone production and rhythmic changes in brain morphology in humans is largely unknown. Here, we examined the relationship between diurnal fluctuations in steroid hormones and multiscale brain morphology in a precision imaging study of a male who completed 40 MRI and serological assessments at 7 A.M. and 8 P.M. over the course of a month, targeting hormone concentrations at their peak and nadir. Diurnal fluctuations in steroid hormones were tied to pronounced changes in global and regional brain morphology. From morning to evening, total brain volume, gray matter volume, and cortical thickness decreased, coincident with decreases in steroid hormone concentrations (testosterone, estradiol, and cortisol). In parallel, cerebrospinal fluid and ventricle size increased from A.M. to P.M. Global changes were driven by decreases within the occipital and parietal cortices. These findings highlight natural rhythms in brain morphology that keep time with the diurnal ebb and flow of steroid hormones.

Information on the associations of testosterone levels with abdominal muscle volume and density in men is limited, while the role of estradiol and SHBG on these muscle characteristics are unclear. Therefore, this study aimed to investigate the association between fasting serum sex hormones and CT-derived abdominal muscle area and radiodensity in adult men. Conducted as a cross sectional observational study using data from the Multi-Ethnic Study of Atherosclerosis, our analyses focused on a community-based sample of 907 men aged 45-84 years, with 878 men having complete data. CT scans of the abdomen were interrogated for muscle characteristics, and multivariable linear regressions were used to test the associations. After adjustment for relevant factors, higher levels of both total testosterone and estradiol were associated with higher abdominal muscle area (1.74, 0.1-3.4, and 1.84, 0.4-3.3, respectively). In the final analyses, levels of total testosterone showed a positive association, while an inverse relationship was observed for SHBG with abdominal muscle radiodensity (0.3, 0.0-0.6, and - 0.33, - 0.6 to - 0.1, respectively). Our results indicate a complex association between sex hormones and abdominal muscle characteristics in men. Specifically, total testosterone and estradiol were associated with abdominal muscle area, while only total testosterone was associated with muscle radiodensity and SHBG was inversely associated with muscle radiodensity.Clinical Trial: NCT00005487.

Androgen deprivation therapy (ADT) forms the cornerstone in the treatment of advanced prostate cancer. However, by suppressing testosterone ADT results in a decrease of skeletal muscle mass. In this narrative review, we explore the magnitude and mechanisms of ADT-induced muscle mass loss and the consequences for muscle strength and physical performance. Subsequently, we elucidate the effectiveness of supervised resistance exercise training as a means to mitigate these adverse effects. Literature shows that resistance exercise training can effectively counteract ADT-induced loss of appendicular lean body mass and decline in muscle strength, while the effect on physical performances is inconclusive. As resistance exercise training is feasible and can be safely implemented during ADT (with special attention for patients with bone metastases), it should be incorporated in standard clinical care for prostate cancer patients (starting) with ADT. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of supraphysiologic administration of testosterone in an early and late model of implant osseointegration in rat tibiae. Materials and Methods: A total of 40 rats were randomly allocated into four groups (n = 10/group), which were divided according to the type of experiment and time of osseointegration: (1) vehicle (14 days), (2) testosterone (14 days), (3) vehicle (42 days), and (4) testosterone (42 days). Testosterone cypionate (7.5 mg/kg) administration started 4 weeks before implant placement, and the injections were performed daily until euthanasia. Machined-surface titanium implants (2.2 mm in diameter and 4 mm high) were placed bilaterally in the tibia of animals 28 days after the first testosterone injection. At days 14 and 42 after implant placement, euthanasia was performed and the tibiae were harvested to perform biomechanical evaluation and histomorphometric analysis of bone-to-implant contact (BIC%) and bone between the threads (BBT%). Results: There was no statistical difference in the removal torque of the implants between the groups treated with the vehicle (control group) or testosterone (P > .05). At 14 days of osseointegration, the BIC% and BBT% did not differ between vehicle or testosterone groups (P > .05), while at 42 days, both the BIC% and BBT% were significantly reduced by testosterone compared to the vehicle group (P < .05). Conclusions: Testosterone cypionate in supraphysiologic dose impaired late-phase osseointegration in rat tibiae. [ABSTRACT FROM AUTHOR]

Associations of total testosterone (T) and calculated free T with cardiovascular disease (CVD) remain poorly understood. Particularly how these associations vary according to race and ethnicity in a nationally representative sample of men. Data included 7058 men (≥20 years) from NHANES. CVD was defined as any reported diagnosis of heart failure (HF), coronary artery disease (CAD), myocardial infarction (MI), and stroke. Total T (ng/mL) was obtained among males who participated in the morning examination. Weighted multivariable-adjusted logistic regression models were conducted. We found associations of low T (OR = 1.57, 95% CI = 1.17-2.11), low calculated free T (OR = 1.53, 95% CI = 1.10-2.17), total T (Q1 vs Q5), and calculated free T (Q1 vs Q5) with CVD after adjusting for estradiol and SHBG. In disease specific analysis, low T increased prevalence of MI (OR = 1.72, 95% CI = 1.08-2.75) and HF (OR = 1.74, 95% CI = 1.08-2.82), but a continuous increment of total T reduced the prevalence of CAD. Similar inverse associations were identified among White and Mexican Americans, but not Blacks (OR = 0.93, 95% CI = 0.49-1.76). Low levels of T and calculated free T were associated with an increased prevalence of overall CVD and among White and Mexican Americans. Associations remained in the same direction with specific CVD outcomes in the overall population.

Most of mammalian physiology is under the control of biological rhythms, including the endocrine system with time-varying hormone secretion. Precision neuroimaging studies provide unique insights into how the endocrine system dynamically regulates aspects of the human brain. Recently, we established estrogens ability to drive widespread patterns of connectivity and enhance the global efficiency of large-scale brain networks in a woman sampled every 24 h across 30 consecutive days, capturing a complete menstrual cycle. Steroid hormone production also follows a pronounced sinusoidal pattern, with a peak in testosterone between 6 and 7 A.M. and nadir between 7 and 8 P.M. To capture the brains response to diurnal changes in hormone production, we carried out a companion precision imaging study of a healthy adult man who completed MRI and venipuncture every 12-24 h across 30 consecutive days. Results confirmed robust diurnal fluctuations in testosterone, 17β-estradiol-the primary form of estrogen-and cortisol. Standardized regression analyses revealed widespread associations between testosterone, estradiol, and cortisol concentrations and whole-brain patterns of coherence. In particular, functional connectivity in the Dorsal Attention Network was coupled with diurnally fluctuating hormones. Further, comparing dense-sampling datasets between a man and a naturally cycling woman revealed that fluctuations in sex hormones are tied to patterns of whole-brain coherence in both sexes and to a heightened degree in the male. Together, these findings enhance our understanding of steroid hormones as rapid neuromodulators and provide evidence that diurnal changes in steroid hormones are associated with patterns of whole-brain functional connectivity.

Despite copious data linking brain function with changes to social behavior and mental health, little is known about how puberty relates to brain functioning. We investigated the specificity of brain network connectivity associations with pubertal indices and age to inform neurodevelopmental models of adolescence. We examined how brain network connectivity during a peer evaluation fMRI task related to pubertal hormones (dehydroepiandrosterone and testosterone), pubertal timing and status, and age. Participants were 99 adolescents assigned female at birth aged 9-15 (M = 12.38, SD = 1.81) enriched for the presence of internalizing symptoms. Multivariate analysis revealed that within Salience, between Frontoparietal - Reward and Cinguloopercular - Reward network connectivity were associated with all measures of pubertal development and age. Specifically, Salience connectivity linked with age, pubertal hormones, and status, but not timing. In contrast, Frontoparietal - Reward connectivity was only associated with hormones. Finally, Cinguloopercular - Reward connectivity related to age and pubertal status, but not hormones or timing. These results provide evidence that the salience processing underlying peer evaluation is jointly influenced by various indices of puberty and age, while coordination between cognitive control and reward circuitry is related to pubertal hormones, pubertal status, and age in unique ways.

Friedreich's ataxia (FA) is an autosomal recessive disorder caused by reduced frataxin (FXN) expression in mitochondria, where the lethal component is cardiomyopathy. Using the conditional Fxnflox/null::MCK-Cre knock-out (Fxn-cKO) mouse model, we discovered significant sex differences in the progression towards heart failure, with Fxn-cKO males exhibiting a worse cardiac phenotype, low survival rate, kidney and reproductive organ deficiencies. These differences are likely due to a decline in testosterone in Fxn-cKO males. The decrease in testosterone was related to decreased expression of proteins involved in cholesterol transfer into the mitochondria: StAR and TSPO on the outer mitochondrial membrane, and the cholesterol side-chain cleavage enzyme P450scc and ferredoxin on the inner mitochondrial membrane. Expression of excitation-contraction coupling proteins (L-type calcium channel, RyR2, SERCA2, phospholamban and CaMKIIδ) was decreased significantly more in Fxn-cKO males. This is the first study that extensively investigates the sexual dimorphism in FA mouse model with cardiac calcium signaling impairment.

The field of marine mammal conservation has dramatically benefited from the rapid advancement of methods to assess the reproductive physiology of individuals and populations from steroid hormones isolated from minimally invasive skin-blubber biopsy samples. Historically, this vital information was only available from complete anatomical and physiological investigations of samples collected during commercial or indigenous whaling. Humpback whales (Megaptera novaeangliae) are a migratory, cosmopolitan species that reproduce in warm, low-latitude breeding grounds. New Caledonia is seasonally visited by a small breeding sub-stock of humpback whales, forming part of the endangered Oceania subpopulation. To better understand the demographic and seasonal patterns of reproductive physiology in humpback whales, we quantified baseline measurements of reproductive hormones (progesterone-P4, testosterone-T and 17β-estradiol-E2) using an extensive archive of skin-blubber biopsy samples collected from female humpback whales in New Caledonia waters between 2016 and 2019 (n = 194). We observed significant differences in the P4, T and E2 concentrations across different demographic groups of female humpback whales, and we described some of the first evidence of the endocrine patterns of estrous in live free-ranging baleen whales. This study is fundamental in its methodological approach to a wild species that has a global distribution, with seasonally distinct life histories. This information will assist in monitoring, managing and conserving this population as global ecological changes continue to occur unhindered.