Heritability of testosterone levels in 12-year-old twins and its relation to pubertal development

The aim of this study was to estimate the heritability of variation in testosterone levels in 12-year-old children, and to explore the overlap in genetic and environmental influences on circulating testosterone levels and androgen dependent pubertal development. Midday salivary testosterone samples were collected on two consecutive days in a sample of 183 unselected twin pairs. Androgen induced pubertal development was assessed using self report Tanner scales of pubic hair development (boys and girls) and genital development (boys). A significant contribution of genetic effects to the variance in testosterone levels was found. Heritability was approximately 50% in both boys and girls. The remaining proportion of the variance in testosterone levels could be explained by non-shared environmental influences. The relatively high correlation between testosterone levels of opposite sex dizygotic twins suggests that sex differences in genes influencing variation in testosterone levels have not yet developed in pre- and early puberty. Variance in pubertal development was explained by a large genetic component, moderate shared environmental influences, and a small non-shared environmental effect. Testosterone levels correlated moderately (r = .31) with pubertal development; the covariance between testosterone levels and pubertal development was entirely accounted for by genetic influences

Pathophysiology of Male Hypogonadism Associated with Endogenous Hyperestrogenism — Evidence for Dual Defects in the Gonadal Axis

FEMINIZING tumors of the adrenal cortex are associated with symptoms that presumably reflect the combined effects of estrogen excess and androgen deficiency — gynecomastia, diminished libido, attenuated potency, and testicular and prostatic atrophy.1 2 3 4 5 Although such tumors are extremely rare, they provide a unique opportunity to appraise the nature of endogenous estrogen action on the gonadal axis in men. In principle, the pathophysiologic effects of estrogen hypersecretion could be expressed at the level of either the Leydig cell or the hypothalamic–pituitary axis (or both), with consequent suppression of androgen production. In the present studies, we investigated the endocrine consequences of reversible endogenous estrogen excess in a patient with a surgically resectable feminizing adrenal cortical tumor

Effect of local cold-pack application on systemic anabolic and inflammatory response to sprint-interval training: a prospective comparative trial

We evaluated the effect of cold ice-pack application following a brief sprint-interval training on the balance between anabolic mediators [growth hormone (GH), insulin-like growth factor-I (IGF-I), testosterone], catabolic markers (cortisol, IGFBP-1), and circulating pro [Interlukin-6 (IL-6) and IL-1β]- and anti-inflammatory cytokines [IL-1 receptor antagonist (IL-1ra)]. Twelve males, elite junior handball players performed 4 × 250 m treadmill run, at 80% of each individual’s maximal speed, followed by a rest period with and without local cold-pack application. Pre, immediately post, and 60-min post-exercise blood samples were drawn. Exercise was associated with a significant increase in IL-6, GH, IGFBP-3, and testosterone levels. Local cold-pack application was associated with significant decreases in IL-1β, IL-1ra, IGF-I, and IGFBP-3 and a greater increase of IGFBP-1 during recovery. Local ice therapy immediately following sprint-interval training was associated with greater decreases in both pro- and anti-inflammatory cytokines and anabolic hormones supporting some clinical evidence for possible negative effects on athletic performance

Association of adiposity and mental health functioning across the lifespan:Findings from understanding society (The UK household longitudinal study)

Background: Evidence on the adiposity-mental health associations is mixed, with studies finding positive, negative or no associations, and less is known about how these associations may vary by age. Objective: To examine the association of adiposity -body mass index (BMI), waist circumference (WC) and percentage body fat (BF%)- with mental health functioning across the adult lifespan. Methods: Data from 11,257 participants (aged 18+) of Understanding Society: the UK Household Longitudinal Study (waves 2 and 3, 5/2010-7/2013) were employed. Regressions of mental health functioning, assessed by the Mental Component Summary (MCS-12) and the General Health Questionnaire (GHQ-12), on adiposity measures (continuous or dichotomous indicators) were estimated adjusted for covariates. Polynomial age-adiposity interactions were estimated. Results: Higher adiposity was associated with poorer mental health functioning. This emerged in the 30s, increased up to mid-40s (all central adiposity and obesity-BF% measures) or early 50s (all BMI measures) and then decreased with age. Underlying physical health generally accounted for these associations except for central adiposity, where associations remained statistically significant from the mid-30s to50s. Cardiovascular, followed by arthritis and endocrine, conditions played the greatest role in attenuating the associations under investigation. Conclusions: We found strong age-specific patterns in the adiposity-mental health functioning association that varied across adiposity measures. Underlying physical health had the dominant role in attenuating these associations. Policy makers and health professionals should target increased adiposity, mainly central adiposity, as it is a risk factor for poor mental health functioning in those aged between mid-30s to 50 years

Angiotensin II Requires Zinc and Downregulation of the Zinc Transporters ZnT3 and ZnT10 to Induce Senescence of Vascular Smooth Muscle Cells

Senescence, a hallmark of mammalian aging, is associated with the onset and progression of cardiovascular disease. Angiotensin II (Ang II) signaling and zinc homeostasis dysfunction are increased with age and are linked to cardiovascular disease, but the relationship among these processes has not been investigated. We used a model of cellular senescence induced by Ang II in vascular smooth muscle cells (VSMCs) to explore the role of zinc in vascular dysfunction. We found that Ang II-induced senescence is a zinc-dependent pathway mediated by the downregulation of the zinc transporters ZnT3 and ZnT10, which work to reduce cytosolic zinc. Zinc mimics Ang II by increasing reactive oxygen species (ROS), activating NADPH oxidase activity and Akt, and by downregulating ZnT3 and ZnT10 and inducing senescence. Zinc increases Ang II-induced senescence, while the zinc chelator TPEN, as well as overexpression of ZnT3 or ZnT10, decreases ROS and prevents senescence. Using HEK293 cells, we found that ZnT10 localizes in recycling endosomes and transports zinc into vesicles to prevent zinc toxicity. Zinc and ZnT3/ZnT10 downregulation induces senescence by decreasing the expression of catalase. Consistently, ZnT3 and ZnT10 downregulation by siRNA increases ROS while downregulation of catalase by siRNA induces senescence. Zinc, siZnT3 and siZnT10 downregulate catalase by a post-transcriptional mechanism mediated by decreased phosphorylation of ERK1/2. These data demonstrate that zinc homeostasis dysfunction by decreased expression of ZnT3 or ZnT10 promotes senescence and that Ang II-induced senescence is a zinc and ROS-dependent process. Our studies suggest that zinc might also affect other ROS-dependent processes induced by Ang II, such as hypertrophy and migration of smooth muscle cells

Childhood Obesity

In March 2004 a group of 65 physicians and other health professionals representing nine countries on four continents convened in Israel to discuss the widespread public health crisis in childhood obesity. Their aim was to explore the available evidence and develop a consensus on the way forward. The process was rigorous, although time and resources did not permit the development of formal evidence-based guidelines. In the months before meeting, participants were allocated to seven groups covering prevalence, causes, risks, prevention, diagnosis, treatment, and psychology. Through electronic communication each group selected the key issues for their area, searched the literature, and developed a draft document. Over the 3-d meeting, these papers were debated and finalized by each group before presenting to the full group for further discussion and agreement. In developing a consensus statement, this international group has presented the evidence, developed recommendations, and provided a platform aimed toward future corrective action and ongoing debate in the international community

Reversible Congenital Hypogonadotropic Hypogonadism in Patients with CHD7, FGFR1 or GNRHR Mutations

Peer reviewe