Adrenarcheal hormone-related development of white matter during late childhood.

The aim of the current study was to longitudinally examine how adrenarcheal hormones influence the development of white matter structure from age 8.5 to 10 years. Participants were 120 children (66 female; mean age 8.45 years at Time 1 and 9.97 years at Time 2) who completed two diffusion-weighted imaging scans 1.5 years apart. Morning saliva samples were taken at both assessment time points to measure levels of dehydroepiandrosterone (DHEA), its sulphate (DHEAS), and testosterone. Fixel-based analysis was performed to examine how changes in white matter fibre density (FD) and cross-section (FC) over time were associated with initial levels of hormones, and changes in hormone levels over time. Both FD and FC increased over time in a wide range of white matter tracts. Increases in testosterone over time were related to relatively weaker increases in FC in the inferior fronto-occipital fasciculus. Levels and change in DHEA and DHEAS were not related to FD or FC changes. The results demonstrated development of white matter fibre density and cross-section from age 8.5 to 10 years. Changes in adrenarcheal hormone levels showed limited, localized associations with development of white matter FC. Future research should examine the relevance of adrenarcheal hormone-related white matter development for cognitive functioning; as well as directly compare analysis techniques of white matter structure.

Anabolic steroids and tendons: A review of their mechanical, structural, and biologic effects.

One of the suspected deleterious effects of androgenic-anabolic steroids (AAS) is the increased risk for tendon rupture. However, investigations to date have produced inconsistent results and it is still unclear how AAS influence tendons. A systematic review of the literature was conducted to identify studies that have investigated the mechanical, structural, or biologic effects that AAS have on tendons. In total, 18 highly heterogeneous studies were identified. Small animal studies made up the vast majority of published research, and contradictory results were reported frequently. All of the included studies focused on the potential deleterious effects that AAS have on tendon, which is striking given the recent use of AAS in patients following tendon injury. Rather than providing strong evidence for or against the use of AAS, this review highlights the need for additional research. Future studies investigating the use of AAS as a possible treatment for tendon injury/pathology are supported by reports suggesting that AAS may counteract the irreparable structural/functional changes that occur in the musculotendinous unit following rotator cuff tears, as well as studies suggesting that the purported deleterious effects on tendon may be transient. Other possible areas for future research are discussed in the context of key findings that may have implications for the therapeutic application of AAS. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2830-2841, 2018.

Androgens regulate TRAIL-induced cell death in prostate cancer cells via multiple mechanisms.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising therapeutic agent for prostate cancer because it selectively induces apoptosis in cancer cells but not in normal cells. Previous reports have suggested that androgens regulate TRAIL-induced apoptosis in prostate cancer cells. However, there are discrepancies between these reports of how androgens affect TRAIL-induced cell death. To clarify the role of androgens on TRAIL-induced apoptosis in prostate cancer cells, we investigated the effects of androgen on TRAIL-induced cell death in a dose-response manner. Our results showed that although androgens sensitize LNCaP cells to TRAIL-induced apoptosis, this effect is dose-dependent and biphasic. We found that low levels of androgen are superior to high levels of androgen in term of sensitizing LNCaP cells to TRAIL. We also found that upregulation of DR5 (TRAIL-R2) expression by androgens is critical for sensitizing LNCaP cells to TRAIL. However, low levels of androgen are sufficient to induce DR5 expression and sensitize LNCaP cells to TRAIL-induced cell death. High levels of androgen alter the TRADD/RIP1 ratio, which may contribute to NF-κB activation and sequentially inhibit TRAIL-induced apoptosis.

Androgen up-regulates vascular endothelial growth factor expression in prostate cancer cells via an Sp1 binding site.

BACKGROUND: Vascular Endothelial Growth Factor (VEGF) is regulated by a number of different factors, but the mechanism(s) behind androgen-mediated regulation of VEGF in prostate cancer are poorly understood. RESULTS: Three novel androgen receptor (AR) binding sites were discovered in the VEGF promoter and in vivo binding of AR to these sites was demonstrated by chromatin immunoprecipitation. Mutation of these sites attenuated activation of the VEGF promoter by the androgen analog, R1881 in prostate cancer cells. The transcription factors AR and Sp1 were shown to form a nuclear complex and both bound the VEGF core promoter in chromatin of hormone treated CWR22Rv1 prostate cancer cells. The importance of the Sp1 binding site in hormone mediated activation of VEGF expression was demonstrated by site directed mutagenesis. Mutation of a critical Sp1 binding site (Sp1.4) in the VEGF core promoter region prevented activation by androgen. Similarly, suppression of Sp1 binding by Mithramycin A treatment significantly reduced VEGF expression. CONCLUSIONS: Our mechanistic study of androgen mediated induction of VEGF expression in prostate cancer cells revealed for the first time that this induction is mediated through the core promoter region and is dependent upon a critical Sp1 binding site. The importance of Sp1 binding suggests that therapy targeting the AR-Sp1 complex may dampen VEGF induced angiogenesis and, thereby, block prostate cancer progression, helping to maintain the indolent form of prostate cancer.

Brachyhypopomus draco, a new sexually dimorphic species of Neotropical electric fish from southern South America (Gymnotiformes: Hypopomidae)

Brachyhypopomus draco, new species, is described from central, southern and coastal regions of Rio Grande do Sul state, Brazil, and Uruguay. It is diagnosed from congeners by, among other characters, the shape of the distal portion of the caudal filament in mature males, which during the reproductive period forms a distinct paddle shape structure.

Brachyhypopomus draco, espécie nova, é descrita para as regiões central, sul e costeira do estado do Rio Grande do Sul, Brasil, e Uruguai. Ela é diagnosticada de seus congêneres, entre outros caracteres, pela porção final do filamento caudal de machos maduros, que adquire a forma de um remo durante o período reprodutivo.