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#34847080 2021/11/30 To Up
Diminished androgen levels are linked to irritable bowel syndrome and cause bowel dysfunction in mice.Functional gastrointestinal disorders (FGIDs) have prominent sex differences in incidence, symptoms, and treatment response that are not well understood. Androgens are steroid hormones present at much higher levels in males than females and could be involved in these differences. In adults with irritable bowel syndrome (IBS), a FGID that affects 5-10% of the population worldwide, we found that free testosterone levels were lower than those in healthy controls and inversely correlated with symptom severity. To determine how this diminished androgen signaling could contribute to bowel dysfunction, we depleted gonadal androgens in adult mice and found that this caused a profound deficit in gastrointestinal transit. Restoring a single androgen hormone was sufficient to rescue this deficit, suggesting that circulating androgens are essential for normal bowel motility in vivo. To determine the site of action, we probed androgen receptor expression in the intestine and discovered, unexpectedly, that a large subset of enteric neurons became androgen-responsive upon puberty. Androgen signaling to these neurons was required for normal colonic motility in adult mice. Taken together, these observations establish a role for gonadal androgens in the neural regulation of bowel function and link altered androgen levels with a common digestive disorder.
Daniella Rastelli, Ariel Robinson, Valentina N Lagomarsino, Lynley T Matthews, Rafla Hassan, Kristina Perez, William Dan, Peter D Yim, Madison Mixer, Aleksandra Prochera, Amy Shepherd, Liang Sun, Kathryn Hall, Sarah Ballou, Anthony Lembo, Judy Nee, Meenakshi Rao
1302 related Products with: Diminished androgen levels are linked to irritable bowel syndrome and cause bowel dysfunction in mice.100 1 kit100 mg96 wells501 mg50 ug 100 μg0.1 mg200ug100ul100ug
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#34843781 2021/11/26 To Up
In vitro profiling of toxic effects of environmental polycyclic aromatic hydrocarbons on nuclear receptor signaling, disruption of endogenous metabolism and induction of cellular stress.Polycyclic aromatic hydrocarbons (PAHs) may interact with multiple intracellular receptors and related signaling pathways. We comprehensively evaluated the toxicity profiles of six environmentally relevant PAHs differing in structure, genotoxicity and their ability to activate the aryl hydrocarbon receptor (AhR). We focused particularly on their impact on intracellular hormone-, xenobiotic- and lipid-sensing receptors, as well as on cellular stress markers, combining a battery of human reporter gene assays and qRT-PCR evaluation of endogenous gene expression in human hepatocyte-like HepaRG cells, with LC/MS-MS analysis of cellular sphingolipids. The effects of PAHs included: activation of estrogen receptor Î± (in case of fluoranthene (Fla), pyrene (Pyr), benz[a]anthracene (BaA), benzo[a]pyrene (BaP)), suppression of androgen receptor activity (Fla, BaA, BaP and benzo[k]fluoranthene (BkF)), enhancement of dexamethasone-induced glucocorticoid receptor activity (chrysene (Chry), BaA, and BaP), or potentiation of triiodothyronine-induced thyroid receptor Î± activity (all tested PAHs). PAHs also induced transcription of endogenous gene targets of constitutive androstane receptor (Fla, Pyr), or repression of target genes of pregnane X receptor and peroxisome proliferator-activated receptor Î± (in case of the AhR-activating PAHs - Chry, BaA, BaP, and BkF) in HepaRG cells. In the same cell model, the AhR agonists reduced the expression of glucose metabolism genes (PCK1, G6PC and PDK4), and they up-regulated levels of glucosylceramides, together with a concomitant induction of expression of UGCG, glucosylceramide synthesis enzyme. Finally, both BaP and BkF were found to induce expression of early stress and genotoxicity markers: ATF3, EGR1, GDF15, CDKN1A/p21, and GADD45A mRNAs, while BaP alone increased levels of IL-6 mRNA. Overall, whereas low-molecular-weight PAHs exerted significant effects on nuclear receptors (with CYP2B6 induction observed already at nanomolar concentrations), the AhR activation by 4-ring and 5-ring PAHs appeared to be a key mechanism underlying their impact on nuclear receptor signaling, endogenous metabolism and induction of early stress and genotoxicity markers.
PavlÃna Å imeÄkovÃ¡, KateÅina PÄnÄÃkovÃ¡, Ondrej KovÃ¡Ä, Josef SlavÃk, Martina PaÅenicovÃ¡, Jan VondrÃ¡Äek, Miroslav Machala
2562 related Products with: In vitro profiling of toxic effects of environmental polycyclic aromatic hydrocarbons on nuclear receptor signaling, disruption of endogenous metabolism and induction of cellular stress.5 G2 Pieces/Box50 ug2 Pieces/Box2 Pieces/Box100ug5mg100ul100ug Lyophilized
#34843630 2021/11/29 To Up
Combination therapy with novel androgen receptor antagonists and statin for castration-resistantÂ prostate cancer.One of the growth mechanisms of castration-resistant prostate cancer (CRPC) is de novo androgen synthesis from intracellular cholesterol, and statins may be able to inhibit this mechanism. In addition, statins have been reported to suppress the expression of androgen receptors (ARs) in prostate cancer cell lines. In this study, we investigated a combination therapy of novel AR antagonists and statin, simvastatin, for CRPC.
Hiroshi Nakayama, Yoshitaka Sekine, Daisuke Oka, Yoshiyuki Miyazawa, Seiji Arai, Hidekazu Koike, Hiroshi Matsui, Yasuhiro Shibata, Kazuhiro Suzuki