Healthy adult men typically produce approximately 3–10 mg of testosterone per day
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shared by Nathan Goodyear on 05 Oct 16
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Androgen deprivation promotes intratumoral synthesis of dihydrotestosterone from androg... - 0 views
www.nature.com/srep01528
androgen metabolites prostate prostate cancer hormones DHT dihydrotestosterone
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shared by Nathan Goodyear on 30 Apr 13
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The Effects of Injected Testosterone Dose and Age on the Conversion of Testosterone to ... - 0 views
www.ncbi.nlm.nih.gov/...PMC2913038
testosterone testosterone therapy low T low Testosterone aromatase Estradiol E2:T
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shared by Nathan Goodyear on 18 May 16
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Extranuclear Actions of the Androgen Receptor Enhance Glucose-Stimulated Insulin Secret... - 0 views
www.cell.com/...S1550-4131(16)30118-8
Testosterone low Testosterone low T hormones male hormones DHT dihydrotestosterone insulin AR androgen receptor Diabetes
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only abstract available here. Mouse model finds possible explanation for low Testosterone and diabetes link. Actually, the link is between the metabolite DHT and the AR. The activity of AR from DHT binding induces beta cell insulin secretion in the presence of glucose. This is dependent on glucagon-like peptide 1 receptor activation also, which AR activation by DHT does in fact do.
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shared by Nathan Goodyear on 28 Sep 16
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Chemistry and Structural Biology of Androgen Receptor - 0 views
www.ncbi.nlm.nih.gov/...PMC2096617
androgens Testosterone DHT dihydrotestosterone AR androgen receptors male hormones hormones
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5α-DHT is only about 5% as abundant in the blood as testosterone and is largely derived from peripheral metabolism of testosterone
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Approximately 90% of an oral dose of testosterone is metabolized before it reaches the systemic circulation
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there are three modes of action of testosterone. It may directly act through AR in target tissues where 5α-reductase is not expressed, be converted to 5α-DHT (5–10%) by 5α-reductase before binding to AR, or be aromatized to estrogen (0.2%) and act through the estrogen receptor
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estrogen plays a major role in regulating metabolic process,74,75 mood and cognition,76 cardiovascular disease,77,78 sexual function including libido,79 and bone turnover in men
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testosterone is the major androgen that acts in the “DHT-independent” tissues, such as skeletal muscle, where 5α-reductase is not expressed or is expressed at a very low level
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A Double-Blind, Placebo-Controlled, Randomized Clinical Trial of Transdermal Dihydrotes... - 0 views
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A double-blind, placebo-controlled, ran - PubMed Mobile - 0 views
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TBioMed | Full text | The Estradiol-Dihydrotestosterone model of prostate cancer - 0 views
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shared by Nathan Goodyear on 20 Feb 12
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Progesterone metabolites in breast cancer - 1 views
erc.endocrinology-journals.org/...717.full
progesterone metabolism tumor tumorigenesis cancer risk growth hormone hormones 5-beta-pregnanediol 5-alpha-pregnanediol 4-pregnenediol 5-alpha reductase
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P metabolites produced within breast tissues might be independently active hormones functioning as cancer-promoting or -inhibiting regulatory agents
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these P metabolites function as independent pro-or anti-cancer autocrine/paracrine hormones that regulate cell proliferation, adhesion, apoptosis and cytoskeletal, and other cell status molecules via novel receptors located in the cell membrane and intrinsically linked to cell signaling pathways
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only a fraction of all breast cancer patients respond to this estrogen-based therapy and the response is only temporary
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P serves as the precursor for the major steroid hormones (androgens, estrogens, corticosteroids) produced by the gonadal and adrenal cortical tissues.
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These P-metabolizing enzymes included 5α-reductase, 5β-reductase, 3α-hydroxysteroid oxido-reductase (3α-HSO), 3β-HSO, 20α-HSO, 20β-HSO, 6α(β)-, 11β-, 17-, and 21-hydroxylase, and C17–20-lyase
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Reduction of P to 5α-pregnanes is catalyzed by 5α-reductase and the direct 5α-reduced metabolite of P is 5α-pregnane-3,20-dione (5αP). The 5α-reductase reaction is irreversible
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The two 4-pregnenes resulting from direct P conversion are 4-pregnen-3α-ol-20-one (3αHP) and 4-pregnen-20α-ol-3-one (20αHP), catalyzed by the actions of 3α-HSO and 20α-HSO respectively
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the P-metabolizing enzyme activities identified in human breast tissues and cell lines were: 5α-reductase, 3α-HSO, 3β-HSO, 20α-HSO, and 6α-hydroxylase
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In normal breast tissue, conversion to 4-pregnenes greatly exceeded the conversion to 5α-pregnanes, whereas in tumorous tissue, conversion to 5α-pregnanes greatly exceeded that to 4-pregnenes
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The results indicated that P 5α-reductase activity is significantly higher, whereas P 3α-HSO and 20α-HSO activities are significantly lower in tumor than in normal tissues
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he results showed that production of 5α-pregnanes was higher and that of 4-pregnenes was lower in tumorigenic (e.g. MCF-7) than in nontumorigenic (e.g. MCF-10A) cells (Fig. 3c⇑), while differences in ER/P status did not appear to play a role
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The 5α-pregnane-to-4-pregnene ratios were 7- to 20-fold higher in the tumorigenic than in the nontumorigenic cell lines
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altered direction in P metabolism, and hence in metabolite ratios, was due to significantly elevated 5α-reductase and depressed 3α- and 20α-HSO activities in breast tumor tissues and tumorigenic cells. It appeared, therefore, that changes in P-metabolizing enzyme activities might be related to the shift toward mammary cell tumorigenicity and neoplasia
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In vivo, changes in enzyme activity can result from changes in levels of the enzyme due to changes in expression of the mRNA coding for the enzyme, or from changes in the milieu in which the enzyme operates (such as temperature and pH, and concentrations of cofactors, substrates, products, competitors, ions, phospholipids, and other molecules)
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Overall, the enzyme activity and expression studies strongly suggest that 5α-reductase stimulation and 3α- and 20α-HSO suppression are associated with the transition from normalcy to cancer of the breast
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The level of expression of 5α-reductase is up-regulated by estradiol and P in the uterus (Minjarez et al. 2001) and by 5α-dihydrotestosterone (DHT) in the prostate
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Stimulation in cell numbers was also observed when cells were treated with other 5α-pregnanes, such as 5α-pregnan-3α-ol-20-one, 5α-pregnan-20α-ol-3-one, and 5α-pregnane-3α,20α-diol, whereas other 4-pregnenes such as 20α-HP and 4-pregnene-3α,20α-diol resulted in suppression of cell proliferation
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Stimulation of cell proliferation with 5αP and inhibition with 3αHP were also observed in all other breast cell lines examined, whether ER/P-negative (MCF-10A, MDA-MB-231) or ER/P-positive (T47D, ZR-75-1) and whether requiring estrogen for tumorigenicity (MCF-7, T47D) or not (MDA-MB-231), or whether they are nontumorigenic (
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αHP resulted in significant increases in apoptosis and decreases in mitosis, leading to significant decreases in total cell numbers. In contrast, treatment with 5αP resulted in decreases in apoptosis and increases in mitosis.
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The opposing actions of 5αP and 3αHP on both cell anchorage and proliferation strengthen the hypothesis that the direction of P metabolism in vivo toward higher 5α-pregnane and lower 4-pregnene concentrations could promote breast neoplasia and lead to malignancy.
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The studies showed that binding of 5αP or 3αHP occurs in the plasma membrane fractions, but not in the nuclear or cytosolic compartments
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separate high-specificity, high-affinity, low- capacity receptors for 5αP and 3αHP that are distinct from each other and from the well-studied nuclear/cytosolic P, estrogen, and androgen and corticosteroid receptors
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The studies thus provided the first demonstration of the existence of specific P metabolite receptors
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the receptor results suggest that the putative tumorigenic actions of 5αP may be significantly augmented by the estradiol-induced increases in 5αP binding and decreases in 3αHP binding.
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Estradiol and 5αP resulted in significant dose-dependent increases, whereas 3αHP and 20αHP each resulted in dose-dependent decreases in total ER
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In combination, estradiol + 5αP or 3αHP + 20αHP resulted in additive increases or decreases respectively in ER numbers.
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The data suggest that the action of 5αP on breast cancer cells involves modulation of the MAPK signaling pathway
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current evidence does not appear to support the notion that increased 5α-reductase activity/ expression might significantly alter androgen influences on breast tumor growth.
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Increased muscular dehydroepiandrosterone levels are associated with improved hyperglyc... - 0 views
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Effect of aging on endogenous level of 5 alpha-dihydrotestosterone, testosterone, estra... - 0 views
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Men with BPH found to have higher levels of stromal Estradiol and Estrone. This is associated with aging. This elevation was not found in the prostate epithelium. No correlation with Testosterone and the stroma and epithelium were found. So, the point is that what is happening in the prostate appears to be related to increased aromatase activity in the prostate. Which this has been shown to be evident in the lateral lobes of the prostate in other studies. But DHT? The numbers here are slightly elevated. BUt the balance of DHT to Estradiol may be more important than the individual levels. This study was done in humans.
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shared by Nathan Goodyear on 17 Jan 14
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Metabolic effects of testosterone replacement therapy on hypogonadal men with type 2 di... - 0 views
www.ajandrology.com/article.asp
Testosterone therapy diabetes lipids glucose triglycerides men male hormone hormones
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Among diabetic patients, a reduction in sex hormone binding globulin levels induced by insulin resistance leads to a further decline of testosterone levels
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low bioavailable testosterone concentration was related to decreased lean body mass and muscle strength
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Testosterone deficiency has a high prevalence in men with T2DM, and it is also associated with impaired insulin sensitivity, increased percentage body fat, central obesity, dyslipidemia, hypertension and cardiovascular diseases (CVD)
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A meta-analysis of four randomized controlled trials (RCTs) showed that TRT seemed to improve glycemic control as well as fat mass in T2DM subjects with low testosterone levels and sexual dysfunction.
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Insulin stimulates glucose uptake into muscle and adipose tissue via the Glut4 glucose transporter isoform. When insulin activates signaling via the insulin receptor, Glut4 interacts with insulin receptor substrate 1 to initialize intracellular signaling and facilitate glucose transportation into the cell
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The benefits of TRT on glucose metabolism can mainly be explained by its influence on the insulin signaling pathway
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Insulin resistance as assessed by, which is calculated from the equation (If*Gf/22.5, where If is fasting insulin and Gf is fasting glucose), was definitely improved by TRT after testosterone administration in three studies
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Testosterone was observed to elevate the expression levels and stimulate translocation of Glut4 in cultured skeletal muscle cells and to upregulate Glut4 by activating insulin receptor signaling pathways in neonatal rats
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These effects were inhibited by a dihydrotestosterone (DHT) blocker, indicating that glucose uptake may correlate with conversion of testosterone to DHT and activation of the androgen receptor.
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TRT has been reported to have a positive effect in the decrease of total and LDL cholesterol levels and triglycerides in hypogonadal men
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Epidemiological studies have found a negative relationship between testosterone levels and typical cardiovascular risk markers, such as body mass index, waist circumference, visceral adiposity and carotid intima-media thickness.
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Testosterone treatment was shown to raise hemoglobin, hematocrit and thromboxane, all of which might give rise to CVD
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Low Testosterone is a very significant problem in men with type II Diabetes. Estimated to reach 40%, likely much higher. They based these estimates only on T levels and sexual symptoms. Testosterone improves glycemic control primarily through Increased transcription and transloction of GLUT4 insulin receptors to the cell surface. Inflammation reduction is also a mechanism. Testosteorne lowers Triglycerides in the traditional lipid profile. Studies are mixed on the other aspects of lipids.
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shared by Nathan Goodyear on 15 Jan 14
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Lowered testosterone in male obesity: Mechanisms, morbidity and management Tang Fui MN,... - 0 views
www.ajandrology.com/article.asp
Testosterone male obesity overweight men hormone hormones low T Low T
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The number of overweight people is expected to increase from 937 million in 2005 to 1.35 billion in 2030
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Similarly the number of obese people is projected to increase from 396 million in 2005 to 573 million in 2030
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By 2030, China alone is predicted to have more overweight men and women than the traditional market economies combined
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diacylglycerol O-acyltransferase 2 (DGAT2), mechanistically implicated in this differential storage, [10] is regulated by dihydrotestosterone, [11] suggesting a potential role for androgens to influence the genetic predisposition to either the MHO or MONW phenotype.
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The fact that obese men have lower testosterone compared to lean men has been recognized for more than 30 years
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epidemiological data suggest that the single most powerful predictor of low testosterone is obesity, and that obesity is a major contributor of the age-associated decline in testosterone levels.
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obesity blunts this LH rise, obesity leads to hypothalamic-pituitary suppression irrespective of age which cannot be compensated for by physiological mechanisms
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Reductions in total testosterone levels are largely a consequence of reductions in sex hormone binding globulin (SHBG) due to obesity-associated hyperinsulinemia
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although controversial, measurement of free testosterone levels may provide a more accurate assessment of androgen status than the (usually preferred) measurement of total testosterone in situations where SHBG levels are outside the reference range
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marked obesity however is associated with an unequivocal reduction of free testosterone levels, where LH and follicle stimulating hormone (FSH) levels are usually low or inappropriately normal, suggesting that the dominant suppression occurs at the hypothalamic-pituitary level
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adipose tissue, especially when in the inflamed, insulin-resistant state, expresses aromatase which converts testosterone to estradiol (E 2 ). Adipose E 2 in turn may feedback negatively to decrease pituitary gonadotropin secretion
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In addition to E 2 , increased visceral fat also releases increased amounts of pro-inflammatory cytokines, insulin and leptin; all of which may inhibit the activity of the HPT axis at multiple levels
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In the prospective Massachusetts Male Aging Study (MMAS), moving from a non-obese to an obese state resulted in a decline of testosterone levels
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weight loss, whether by diet or surgery, increases testosterone levels proportional to the amount of weight lost
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Testosterone enhances catecholamine-induced lipolysis in vitro and reduces lipoprotein lipase activity and triglyceride uptake in human abdominal adipose tissue in vivo
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in men with prostate cancer receiving 12 months of androgen deprivation therapy, fat mass increased by 3.4 kg and abdominal VAT by 22%, with the majority of these changes established within 6 months
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increasing body fat suppresses the HPT axis by multiple mechanisms [30] via increased secretion of pro-inflammatory cytokines, insulin resistance and diabetes; [19],[44] while on the other hand low testosterone promotes further accumulation of total and visceral fat mass, thereby exacerbating the gonadotropin inhibition
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men undergoing androgen depletion for prostate cancer show more marked increases in visceral compared to subcutaneous fat following treatment
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androgens can act via the PPARg-pathway [37] which is implicated in the differentiation of precursor fat cells to the energy-consuming phenotype
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low testosterone may compound the effect of increasing fat mass by making it more difficult for obese men to lose weight via exercise
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pro-inflammatory cytokines released by adipose tissue may contribute to loss of muscle mass and function, leading to inactivity and further weight gain in a vicious cycle
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Sarcopenic obesity, a phenotype recapitulated in men receiving ADT for prostate cancer, [55] may not only be associated with functional limitations, but also aggravate the metabolic risks of obesity;
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observational evidence associating higher endogenous testosterone with reduced loss of muscle mass and crude measures of muscle function in men losing weight
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A number of intervention studies have confirmed that both diet- and surgically-induced weight losses are associated with increased testosterone, with the rise in testosterone generally proportional to the amount of weight lost
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shared by Nathan Goodyear on 03 Feb 14
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JCI - Alteration in the metabolism of dihydrotestosterone in elderly men with prostate ... - 0 views
www.jci.org/...pdf
DHT metabolite metabolites 3 alpha-androstanediol 3-alpha-diol male men hormone hormones metabolism prostate elderly
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shared by Nathan Goodyear on 03 Feb 14
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Potential Prostate Cancer Drug Target: Bioactivation of Androstanediol by Conversion to... - 0 views
clincancerres.aacrjournals.org/...5844.full
prostate cancer DHT metabolite metabolites men male hormone hormones 3-alpha-diol 3-alpha androstanediol
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Article discusses the the conversion of 3-alpha-diol back to DHT and this role in prostate cancer in androgen deprivation therapy. What we now know is that this metabolite interacts with ER alpha receptor to promote proliferation. Carcinogenesis appears to be primarily an estrogen driven process and her in prostate cancer, the androgen metabolites are promoting proliferation through estrogen receptors.
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shared by Nathan Goodyear on 27 Jan 14
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The Androgen Derivative 5α-Androstane-3β,17β-Diol Inhibits Prostate Cancer Ce... - 0 views
cancerres.aacrjournals.org/...5445.short
prostate cancer DHT metabolite 3-alpha androstanediol ER beta ER-beta E-cadherin male hormone hormones men
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the dihydrotestosterone metabolite 5α-androstane-3β,17β-diol (3β-Adiol), a steroid which does not bind androgen receptors, but efficiently binds the estrogen receptor β (ERβ), exerts a potent inhibition of prostate cancer cell migration through the activation of the ERβ signaling
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3β-Adiol, through ERβ, induces the expression of E-cadherin, a protein known to be capable of blocking metastasis formation in breast and prostate cancer cells
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DHT metabolite 3-beta androstanediol inhibits prostate cancer via its interaction with ER beta not AR. This study finds increased E-cadherin transcription to reduce metastasis. Estrogen was not active, according to this study. This implies that estrogen in early disease may have a different signal than late.
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shared by Nathan Goodyear on 03 Feb 14
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In older men an optimal plasma testo... [J Clin Endocrinol Metab. 2014] - PubMed - NCBI - 0 views
www.ncbi.nlm.nih.gov/...24257908
Testosterone DHT cardiovascular disease heart men estradiol E2 dihydrotestosterone male hormone hormones
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shared by Nathan Goodyear on 03 Feb 14
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Dihydrotestosterone may inhibit hypothalamo-pi... [Neurosci Lett. 2004] - PubMed - NCBI - 0 views
www.ncbi.nlm.nih.gov/...15234470
hormone hormones DHT metabolite metabolites 3-beta androstanediol 3-beta-diol ER estrogen receptor ER beta ER-beta
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shared by Nathan Goodyear on 03 Feb 14
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The Androgen 5α-Dihydrotestosterone and Its Metabolite 5α-Androstan-3β, 17β-D... - 0 views
www.jneurosci.org/...1448.long
DHT metabolite metabolites 3-beta androstanediol 3-beta-diol HPA stress ER estrogen receptor ER beta ER-beta hormone hormones
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