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Nathan Goodyear

Changes in body composition during a... [J Clin Endocrinol Metab. 2002] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...11836291

body composition lean muscle mass obesity weight gain adipose tissue androgen deprivation therapy prostate cancer male men hormone hormones

shared by Nathan Goodyear on 03 Mar 14 - No Cached
  • Nathan Goodyear on 03 Mar 14
     
    Androgen deprivation therapy was found to decrease lean muscle mass and increase abdominal adipose tissue, not visceral.  Significant change in body composition in men depleted of androgens in androgen deprivation therapy.
Nathan Goodyear

Association between endogenous sex steroid hormones and inflammatory biomarkers in US men - 0 views

www.ncbi.nlm.nih.gov/...PMC3812341

low Testosterone Estrogen Estradiol low T Testosterone hormone hormones CRP inflammation SHBG WBC men male

shared by Nathan Goodyear on 28 Apr 15 - No Cached
  • modest statistically significant inverse associations for total and calculated free testosterone, and modest positive associations for total and calculated free estradiol with CRP concentration
  • Estradiol concentrations were also weakly positively associated with WBC count
  • SHBG was weakly inversely associated with WBC
  • ...21 more annotations...
  • An association between testosterone and WBC count was not observed
  • These findings are consistent with the hypothesis that in men higher androgen concentration is anti-inflammatory, and higher estrogen concentration is pro-inflammatory.
  • the probability of elevated CRP concentrations (≥ 3 mg/L) decreased with higher total and calculated free testosterone concentrations, while the probability increased with higher total and calculated free estradiol concentrations
  • there is ample evidence supporting the immunosuppressive effect of androgens
  • The incidence of autoimmune diseases is higher in androgen-deficient men
  • Studies have shown that the induction of hypogonadism in older men is followed by a significant increase in IL-6 concentrations (Khosla et al. 2002), a potent stimulator of inflammation, and that activation of the androgen receptor exerts a direct anti-inflammatory effect
  • It has been suggested that the mechanisms for the immunosuppressive effect of androgens could be either a direct effect on the expression of inflammatory genes (Bellido et al. 1995; Asirvatham et al. 2006), or an indirect effect through inhibition of nuclear factor-kB activation
  • Estradiol is the major biologically active estrogen, and about 80% is formed in adult men from the aromatization of testosterone primarily in the adipose tissue
  • estrogen can stimulate the transcription factor C/EBP-β, which is involved in CRP transcription
  • Most prior cross-sectional studies have observed inverse associations between androgen concentrations and inflammatory biomarkers
  • A recent study in Chinese men showed that lower concentrations of total and calculated free testosterone were associated with higher CRP concentration
  • Data from the Boston Area Community Health Survey also reported inverse associations between testosterone and CRP concentrations
  • Total testosterone was inversely associated with WBC count (Tang et al. 2007; Schneider et al. 2009; Brand et al. 2012), but calculated free testosterone was not associated with WBC
  • The first trial found a decrease in CRP, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNFα) but no changes in IL-6 and IL-10 concentrations between the active treatment and placebo arms
  • the majority of studies in the literature have not observed statistically significant associations between estradiol and inflammatory biomarkers in men, although several of them observed point estimates in the positive direction
  • total testosterone and estradiol compete for binding to SHBG, and seem to have opposite effects on the concentration of inflammatory biomarkers
  • A small randomized controlled trial of estrogen replacement therapy in prostate cancer patients showed an increase in CRP in the active treatment group versus the comparator group
  • Obese men are known to have lower androgen concentrations compared to their normal-weight counterparts
  • The strongest suggestion of an interaction was the inverse association between androstanediol glucuronide and CRP concentrations in obese participants, while the association was positive in the non-obese
  • A recent Chinese cross-sectional study observed stronger inverse associations between total testosterone and CRP concentrations in individuals with a BMI of 27.5 kg/m2 or greater
  • our results suggest that total and calculated free testosterone are modestly inversely associated with CRP concentrations, and that total and calculated free estradiol are modestly positively associated with CRP and WBC
  • Nathan Goodyear on 28 Apr 15
     
    Study results suggest that higher Testosterone and lower Estrogen levels provide anti-inflammatory effects in men.  The inflammatory biomarker assessed here was CRP.  Low total and calculated free Testosterone was associated with an increase in CRP.  In contrast, total and free Estrogen was associated with an increase in CRP.  Estradiol increased WBC count and SHBG was inversely related to WBC count in this study.
Nathan Goodyear

Plant-derived 3,3′-Diindolylmethane Is a Strong Androgen Antagonist in Human ... - 0 views

www.jbc.org/...21136.full

DIM I3C PSA AR androgen receptor prostate cancer men male hormone hormones androgen

shared by Nathan Goodyear on 05 Nov 14 - No Cached
  • Inhibition of Endogenous PSA Expression by DIM
  • DIM strongly inhibited DHT induction of androgen-responsive genes by more than 50%
  • antiandrogenic activity of DIM
  • ...8 more annotations...
  • DIM suppresses DHT-induced cell growth and PSA expression and exhibits no AR agonist activity
  • DIM has a strong affinity for both the mutant AR inLNCaP cells and for recombinant wild-type human AR
  • nuclear translocation and foci formation of DHT-bound AR are inhibited by DIM
  • Our investigation, leads to the conclusion that DIM is a strong, pure androgen antagonist.
  • The down-regulation of PSA by DIM
  • PSA has been reported to promote the proliferation, migration, and metastasis of prostate cancer cells through several mechanisms, including cleavage of insulin-like growth factor-binding protein-3 and degradation of extracellular matrix proteins fibronectin and laminin
  • PSA expression is regulated by the AR and is thought to function as a growth factor in LNCaP cells
  • down-regulation of PSA expression may be important in the antiproliferative effects of DIM in LNCaP cells
  • Nathan Goodyear on 05 Nov 14
     
    DIM, from cruciferous veggies often used to aid estrogen metabolism, is found to decrease PSA transcription and function as an androgen receptor antagonist in prostate cancer cell lines.
Nathan Goodyear

Androgen therapy and atherosclerotic cardiovascular disease - 0 views

www.ncbi.nlm.nih.gov/...PMC2464747

cardiovascular disease hormone hormones men women male female

shared by Nathan Goodyear on 13 Aug 14 - No Cached
  • In women, it is much clearer that androgen excess is linked to the burden of CVD risk factors
  • insulin resistance is a consequence of androgen effects
  • Women with PCOS have a sustained exposure to high physiologic androgen levels. This condition is associated with endothelial dysfunction, obesity and metabolic abnormalities such as insulin resistance and dyslipidaemia
  • ...4 more annotations...
  • Further evidence of a link between high androgen levels and CVD or CVD risk factors is observed in women with polycystic ovary syndrome (PCOS)
  • For T treatment in aging women, the current data would suggest androgen excess has adverse effects on CVD risk factors, especially in women with diabetes
  • androgen use and abuse is increasing in our society, either for therapeutic or recreational reasons
  • For men, exogenous T treatment appears largely beneficial
  • Nathan Goodyear on 13 Aug 14
     
    I love these review articles that highlight the metabolic differences of hormones in women versus men.  The medical community as a whole doesn't seem to get this at all.  The marketing-based medical community doesn't either.
Nathan Goodyear

Testosterone at high concentrations interacts ... [Endocrinology. 1990] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...2298157

DHT testosterone androgen men male hormone hormones receptor receptors androgen receptor androgen receptors

shared by Nathan Goodyear on 28 Nov 12 - No Cached
  • Nathan Goodyear on 28 Nov 12
     
    DHT binds to androgen receptor with higher affinity and stays bound with receptor up to 5 x longer.
Nathan Goodyear

Androgen deprivation therapy in men with prostate cancer: how should the side effects b... - 0 views

onlinelibrary.wiley.com/...full

androgen deprivation therapy Testosterone insulin sensitivity resistance diabetes prostate cancer men male hormone hormones

shared by Nathan Goodyear on 04 Feb 14 - No Cached
  • Nathan Goodyear on 04 Feb 14
     
    Androgen deprivation therapy in men has been shown to worsen insulin resistance and precipitate type II Diabetes as well as stimulate weight gain.  This suggests a cause effect relationship between Testosterone and insulin sensitivity.  Other studies have pointed to a reciprocal decline in Testosterone due to hyperglycemia--both acute and chronic.   Androgen deprivation has a significant long list of cardiovascular risks and this should be discussed with the patient.
Nathan Goodyear

Testosterone and glucose metabolism in men: current concepts and controversies - 0 views

joe.endocrinology-journals.org/...R37.full

Low T Testosterone metabolic syndrome MetS Diabetes men male glucose hormone hormones g

shared by Nathan Goodyear on 04 Feb 14 - No Cached
  • Around 50% of ageing, obese men presenting to the diabetes clinic have lowered testosterone levels relative to reference ranges based on healthy young men
  • The absence of high-level evidence in this area is illustrated by the Endocrine Society testosterone therapy in men with androgen deficiency clinical practice guidelines (Bhasin et al. 2010), which are appropriate for, but not specific to men with metabolic disorders. All 32 recommendations made in these guidelines are based on either very low or low quality evidence.
  • A key concept relates to making a distinction between replacement and pharmacological testosterone therapy
  • ...59 more annotations...
  • The presence of symptoms was more closely linked to increasing age than to testosterone levels
  • Findings similar to type 2 diabetes were reported for men with the metabolic syndrome, which were associated with reductions in total testosterone of −2.2 nmol/l (95% CI −2.41 to 1.94) and in free testosterone
  • low testosterone is more predictive of the metabolic syndrome in lean men
  • Cross-sectional studies uniformly show that 30–50% of men with type 2 diabetes have lowered circulating testosterone levels, relative to references based on healthy young men
  • In a recent cross-sectional study of 240 middle-aged men (mean age 54 years) with either type 2 diabetes, type 1 diabetes or without diabetes (Ng Tang Fui et al. 2013b), increasing BMI and age were dominant drivers of low total and free testosterone respectively.
  • both diabetes and the metabolic syndrome are associated with a modest reduction in testosterone, in magnitude comparable with the effect of 10 years of ageing
  • In a cross-sectional study of 490 men with type 2 diabetes, there was a strong independent association of low testosterone with anaemia
  • In men, low testosterone is a marker of poor health, and may improve our ability to predict risk
    • Nathan Goodyear
      Nathan Goodyear on 04 Feb 14
       
      probably the most important point made in this article
  • low testosterone identifies men with an adverse metabolic phenotype
  • Diabetic men with low testosterone are significantly more likely to be obese or insulin resistant
  • increased inflammation, evidenced by higher CRP levels
  • Bioavailable but not free testosterone was independently predictive of mortality
  • It remains possible that low testosterone is a consequence of insulin resistance, or simply a biomarker, co-existing because of in-common risk factors.
  • In prospective studies, reviewed in detail elsewhere (Grossmann et al. 2010) the inverse association of low testosterone with metabolic syndrome or diabetes is less consistent for free testosterone compared with total testosterone
  • In a study from the Framingham cohort, SHBG but not testosterone was prospectively and independently associated with incident metabolic syndrome
  • low SHBG (Ding et al. 2009) but not testosterone (Haring et al. 2013) with an increased risk of future diabetes
  • In cross-sectional studies of men with (Grossmann et al. 2008) and without (Bonnet et al. 2013) diabetes, SHBG but not testosterone was inversely associated with worse glycaemic control
  • SHBG may have biological actions beyond serving as a carrier protein for and regulator of circulating sex steroids
  • In men with diabetes, free testosterone, if measured by gold standard equilibrium dialysis (Dhindsa et al. 2004), is reduced
    • Nathan Goodyear
      Nathan Goodyear on 04 Feb 14
       
      expensive, laborious process filled with variables
  • Low free testosterone remains inversely associated with insulin resistance, independent of SHBG (Grossmann et al. 2008). This suggests that the low testosterone–dysglycaemia association is not solely a consequence of low SHBG.
  • Experimental evidence reviewed below suggests that visceral adipose tissue is an important intermediate (rather than a confounder) in the inverse association of testosterone with insulin resistance and metabolic disorders.
  • testosterone promotes the commitment of pluripotent stem cells into the myogenic lineage and inhibits their differentiation into adipocytes
  • testosterone regulates the metabolic functions of mature adipocytes (Xu et al. 1991, Marin et al. 1995) and myocytes (Pitteloud et al. 2005) in ways that reduce insulin resistance.
  • Pre-clinical evidence (reviewed in Rao et al. (2013)) suggests that at the cellular level, testosterone may improve glucose metabolism by modulating the expression of the glucose-transported Glut4 and the insulin receptor, as well as by regulating key enzymes involved in glycolysis.
  • More recently testosterone has been shown to protect murine pancreatic β cells against glucotoxicity-induced apoptosis
  • Interestingly, a reciprocal feedback also appears to exist, given that not only chronic (Cameron et al. 1990, Allan 2013) but also, as shown more recently (Iranmanesh et al. 2012, Caronia et al. 2013), acute hyperglycaemia can lower testosterone levels.
  • There is also evidence that testosterone regulates insulin sensitivity directly and acutely
  • In men with prostate cancer commencing androgen deprivation therapy, both total as well as, although not in all studies (Smith 2004), visceral fat mass increases (Hamilton et al. 2011) within 3 months
  • More prolonged (>12 months) androgen deprivation therapy has been associated with increased risk of diabetes in several large observational registry studies
  • Testosterone has also been shown to reduce the concentration of pro-inflammatory cytokines in some, but not all studies, reviewed recently in Kelly & Jones (2013). It is not know whether this effect is independent of testosterone-induced changes in body composition.
  • the observations discussed in this section suggest that it is the decrease in testosterone that causes insulin resistance and diabetes. One important caveat remains: the strongest evidence that low testosterone is the cause rather than consequence of insulin resistance comes from men with prostate cancer (Grossmann & Zajac 2011a) or biochemical castration, and from mice lacking the androgen receptor.
  • Several large prospective studies have shown that weight gain or development of type 2 diabetes is major drivers of the age-related decline in testosterone levels
  • there is increasing evidence that healthy ageing by itself is generally not associated with marked reductions in testosterone
  • Circulating testosterone, on an average 30%, is lower in obese compared with lean men
  • increased visceral fat is an important component in the association of low testosterone and insulin resistance
  • The vast majority of men with metabolic disorders have functional gonadal axis suppression with modest reductions in testosterone levels
  • obesity is a dominant risk factor
  • men with Klinefelter syndrome have an increased risk of metabolic disorders. Interestingly, greater body fat mass is already present before puberty
  • Only 5% of men with type 2 diabetes have elevated LH levels
  • inhibition of the gonadal axis predominantly takes place in the hypothalamus, especially with more severe obesity
  • Metabolic factors, such as leptin, insulin (via deficiency or resistance) and ghrelin are believed to act at the ventromedial and arcuate nuclei of the hypothalamus to inhibit gonadotropin-releasing hormone (GNRH) secretion from GNRH neurons situated in the preoptic area
  • kisspeptin has emerged as one of the most potent secretagogues of GNRH release
  • hypothesis that obesity-mediated inhibition of kisspeptin signalling contributes to the suppression of the HPT axis, infusion of a bioactive kisspeptin fragment has been recently shown to robustly increase LH pulsatility, LH levels and circulating testosterone in hypotestosteronaemic men with type 2 diabetes
  • A smaller study with a similar experimental design found that acute testosterone withdrawal reduced insulin sensitivity independent of body weight, whereas oestradiol withdrawal had no effects
  • suppression of the diabesity-associated HPT axis is functional, and may hence be reversible
  • Obesity and dysglycaemia and associated comorbidities such as obstructive sleep apnoea (Hoyos et al. 2012b) are important contributors to the suppression of the HPT axis
  • weight gain and development of diabetes accelerate the age-related decline in testosterone
  • Modifiable risk factors such as obesity and co-morbidities are more strongly associated with a decline in circulating testosterone levels than age alone
  • 55% of symptomatic androgen deficiency reverted to a normal testosterone or an asymptomatic state after 8-year follow-up, suggesting that androgen deficiency is not a stable state
  • Weight loss can reactivate the hypothalamic–pituitary–testicular axis
  • Leptin treatment resolves hypogonadism in leptin-deficient men
  • The hypothalamic–pituitary–testicular axis remains responsive to treatment with aromatase inhibitors or selective oestrogen receptor modulators in obese men
  • Kisspeptin treatment increases LH secretion, pulse frequency and circulating testosterone levels in hypotestosteronaemic men with type 2 diabetes
  • change in BMI was associated with the change in testosterone (Corona et al. 2013a,b).
  • weight loss can lead to genuine reactivation of the gonadal axis by reversal of obesity-associated hypothalamic suppression
  • There is pre-clinical and observational evidence that chronic hyperglycaemia can inhibit the HPT axis
  • in men who improved their glycaemic control over time, testosterone levels increased. By contrast, in those men in whom glycaemic control worsened, testosterone decreased
  • testosterone levels should be measured after successful weight loss to identify men with an insufficient rise in their testosterone levels. Such men may have HPT axis pathology unrelated to their obesity, which will require appropriate evaluation and management.
  • Nathan Goodyear on 04 Feb 14
     
    Article discusses the expanding evidence of low T and Metabolic syndrome.
Nathan Goodyear

Access : The effect of diet-induced insulin resistance on DNA methylation of the androg... - 0 views

www.nature.com/...aja201326a.html

androgen receptor AR insulin resistance methylation male hormone hormones

shared by Nathan Goodyear on 26 Aug 13 - No Cached
  • Nathan Goodyear on 26 Aug 13
     
    This study finds that insulin resistance results in methylation of the promoter region for androgen receptor expression, resulting in a decrease in androgen production.
Nathan Goodyear

Letter to the editor - 0 views

onlinelibrary.wiley.com/...j.1464-410X.2010.09526.x.pdf

PSA androgen receptor androgen receptor prostate ER alpha estrogen T:DHT

shared by Nathan Goodyear on 25 Sep 13 - No Cached
  • Nathan Goodyear on 25 Sep 13
     
    Good brief discussion of membrane Androgen receptor and intracellular Androgen receptor as well as the effects of aromatase and ER alpha. The point is that dual actions can be on going in the elevation of PSA values. Rightly so, this short rebuttal points out that a high T/DHT and a high mAR/iAR results in apoptosis.
Nathan Goodyear

Prostate Cancer and Prostatic Diseases - Androgen dynamics and serum PSA in patients tr... - 0 views

www.nature.com/...pcan20148a.html

ADT androgen deprivation therapy male hormone hormones prostate cancer PSA disease

shared by Nathan Goodyear on 31 Mar 14 - No Cached
  • Nathan Goodyear on 31 Mar 14
     
    ADT therapy with abiraterone inhibits androgen production from both testicular and adrenal origins.  This study finds that a decrease in androgen production through ADT did not always equal a decrease in PSA, indicating other mechanisms of prostate cancer profession.
Nathan Goodyear

Clostridium scindens: a human gut microbe with a high potential to convert glucocortico... - 0 views

www.jlr.org/...2437.full

gut microbiota gut microbiome gut bacteria androgens hormones clostridium scindens

shared by Nathan Goodyear on 29 Apr 15 - No Cached
  • During the enterohepatic circulation (EC), bile salts are synthesized in the liver, concentrated in the gallbladder, and function in the lumen of the small intestine to absorb dietary lipids and limit microbial growth at the site of nutrient uptake
  • Bile acid 7α/β-dehydroxylating bacteria are organisms capable of converting primary bile acids made by the host to harmful secondary bile acids, deoxycholic acid, and lithocholic acid
  • These bacteria normally comprise a small proportion of the gut microbiota (∼103–104/g wet weight) and consist of species within the genus Clostridium
  • ...3 more annotations...
  • C. scindens and a small number of species belonging to the genus Clostridium are responsible for significant alterations in the human bile acid pool composition through bile acid 7α/β dehydroxylation
  • bile acids play an important role in maintaining intestinal barrier function as antimicrobial agents in the small bowel (37, 38) and inducers of antimicrobial peptides
  • Perturbations in the biliary bile acid pool composition can be indicative of hepatogastrointestinal diseases such as fat malabsorption (40), gallstones (3), gastrointestinal cancers (41), and possibly type II diabetes
  • Nathan Goodyear on 29 Apr 15
     
    Gut microbiota appears to be source of androgen production that originates from the gut.  Who would have thought that the Gut as an androgen producing endocrine gland.
Nathan Goodyear

Androgen deprivation promotes intratumoral synthesis of dihydrotestosterone from androg... - 0 views

www.nature.com/...srep01528.html

prostate cancer 3-alpha androstanediol 3-beta androstanediol DHT metabolite metabolites

shared by Nathan Goodyear on 27 Jan 14 - No Cached
  • PSA levels in media were increased by 3α-diol
  • Similarly to 3α-diol, 3β-diol also increased PSA levels in media in a concentration-dependent manner
  • intracellular DHT is synthesized from inactive androgen 3α- and 3β-diol via different pathways in prostate cancer cells
  • ...12 more annotations...
    • Nathan Goodyear
      Nathan Goodyear on 15 Jul 15
       
      error in statement: DHT metabolites are not inactive, they just don't activate AR.
  • 3β-diol can be a precursor of DHT in prostate cancer cells.
  • serum 3α-diol G levels reflect the androgen milieu in localized prostate cancer patients receiving ADT
  • A few studies reported that 3β-diol is a potential ligand of estrogen receptor β (ERβ) and has an antiproliferative effect
  • our results revealed that 3β-diol is potentially a precursor of DHT in prostate cancer cells
  • Bauman et al. showed that 3α-diol is inactive at AR, but induces prostate growth
  • Prostate cancer cells promoted synthesis from the DHT metabolite 3α-diol during the long duration of ADT
    • Nathan Goodyear
      Nathan Goodyear on 15 Jul 15
       
      the authors highlight the suggestion is that 3alpha-diol's activity is via 3alpha-HSD, but fail to mention that it is known that 3alpha-diol interacts with the ER-alpha in the prostate.
  • verified the synthesis of DHT from 3α- or 3β-diol via different pathways in prostate cancer cells in this study
  • HSD17B6 expression levels in prostate cancer can be useful for the diagnosis of high-risk prostate cancer
  • serum 3α-diol G levels reflect the adrenal androgen milieu in localized prostate cancer patients
  • 3α- and 3β-diol has a much more significant role in intratumoral androgen metabolism during ADT
  • Nathan Goodyear on 27 Jan 14
     
    DHT metabolites play an important role of intra-prostate DHT synthesis in those following ADT.  This is a proposed mechanism for the failure rate and aggressive nature of prostate cancer that fails ADT.   3-alpha androstanediol is converted via 3 alpha HSD back to DHT.  In contrast, 3-beta androstanediol cannot.
Nathan Goodyear

Diabetic neuropathic pain: a role for testosterone metabolites - 0 views

joe.endocrinology-journals.org/...1.abstract

diabetes neuropathy pain diabetic DHT androgens 3 alpha-androstanediol metabolites Testosterone androgen male hormone hormones

shared by Nathan Goodyear on 24 Mar 14 - No Cached
  • Nathan Goodyear on 24 Mar 14
     
    Great article.  Really shows the depth of the androgens and androgen metabolites in diabetes and diabetic complications.  In this study, DHT and its metabolis 3-alpha androstanediol were shown to reduce inflammation and pain associated with diabetic neuropathy.  Significant reduction in inflammation signaling (IL-1beta, TNF-alpha) was seen as was potential neurodegenerative processes (glutamate release and astrocyte immunoreactivity).
Nathan Goodyear

Dihydrotestosterone upregulates the expression of epidermal growth factor receptor and ... - 0 views

erc.endocrinology-journals.org/...451.short

bladder cancer bladder cancer androgen receptor androgen receptors AR androgen receptor receptors EGFR epidermal growth factor receptor

shared by Nathan Goodyear on 05 Jan 15 - No Cached
  • Nathan Goodyear on 05 Jan 15
     
    Androgen receptors may be associated with bladder cancer progression.  This study finds AR up regulates Epidermal growth factor in bladder cancer cells.
Nathan Goodyear

Effect of bipolar androgen therapy for asymptomatic men with castra... - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...25568070

prostate cancer BAT bipolar androgen therapy PSA AR androgen receptor ADT androgen deprivation therapy men male hormone hormones

shared by Nathan Goodyear on 27 Jan 15 - No Cached
  • Nathan Goodyear on 27 Jan 15
     
    bipolar androgen therapy proposed as a mechanism to restore AR sensitivity in those men with castration resistant prostate cancer.  This was a very small pilot study.  The effects on PSA were limited in effect as all men eventually developed PSA increase
Nathan Goodyear

Spectrum of metabolic dysfunction in relationship with hyperandrogenemia in obese adole... - 0 views

eje-online.org/...1093.long

PCOS polycystic ovarian syndrome CRP inflammation insulin insulin resistance women female hormone hormones androgens Testosterone hyperandrogenism

shared by Nathan Goodyear on 10 Mar 15 - No Cached
  • subjects with hyperandrogenemic phenotypes displayed the greatest degree of hyperinsulinemia, β-cell function, and chronic inflammation
  • The rise in serum androgens is accompanied by excess insulin secretion, suggesting that insulin directly stimulates ovarian androgen production
  • The degree of hyperinsulinemia does not seem to be directly correlated with the development of HS
  • ...7 more annotations...
  • higher androgen and insulin levels stimulate hair growth
  • genetic and epigenetic changes may be involved in the pathogenesis of PCOS
  • HA has been identified as an important risk factor for MS and dyslipidemias in premenopausal women and adolescents
  • In our study, HA was found to be an independent risk factor for MS as previously reported by Coviello et al.
  • obesity and HA, and not insulin resistance, are the major determinants of chronic inflammation and risk of atherosclerosis in adolescents with PCOS
  • use of an inflammation marker may help identify high-risk females with PCOS
  • hyperandrogenemic PCOS phenotypes have greatest degree of hyperinsulinemia, insulin resistance, and inflammation
  • Nathan Goodyear on 10 Mar 15
     
    Elevated androgens are associated increasing insulin, insulin resistance, and inflammation (as measured by CRP).
Nathan Goodyear

High Progesterone Receptor Expression in Prostate Cancer Is Associated with Clinical Fa... - 0 views

www.ncbi.nlm.nih.gov/...PMC4344236

prostate cancer progesterone progesterone receptor hormones cancer prostate

shared by Nathan Goodyear on 03 Jun 18 - No Cached
  • Currently, there is a general agreement of PGR presence in the stromal cells of PCa
  • expressed in both stromal and tumor cells of the PCa tissue
  • In univariate analysis, a high density level of PGR in both TE and TS was associated with CF
  • ...17 more annotations...
  • High density level of PGR in the TE was an independent prognostic factor for CF.
  • Our large-sized study demonstrates a wide distribution of PGR in stromal and epithelial cells of both benign and malignant prostate tissue
  • there seems to be a general agreement of PGR presence in the stromal cells of PCa
  • In line with our findings, several have also reported a high PGR expression in TE of PCa [9,10,23,25]. In contrast, others have demonstrated a total lack of PGR expression in TE
  • the actions of progesterone are tissue specific
  • In our work univariate analysis demonstrated a high PGR expression in TS to be associated with clinical failure in PCa patients. So far we have not yet demonstrated the mechanism underlying this association
  • Several non-genomic proliferative actions of progesterone have been proposed in tumor cells of other organs, including breast [35–37], astrocytoma [38] and osteosarcoma [39] cell lines. However, such results are contradicted by suggestions of anti-proliferative actions of progesterone in endometrial cancer
  • Yu et al. found PGR to be negatively regulating stromal cell proliferation in vitro
  • high PGR density level in TE was associated with CF in patients with Gleason score ≥ 7
  • Bonkhoff et al. have suggested progressive emergence of PGR during PCa progression and metastasis
  • Latil and co-workers found a decreased PGR expression in clinically localized tumors and increased PGR expression in hormone-refractory tumors, when compared with normal prostate tissue
  • Our findings provide further support to these findings, indicating that PGR plays a role in the pathogenesis of PCa
  • Ki67 and PGR in TE were correlated with CF (S3 Text), indicating an association between PGR and proliferative activity
  • The mechanism behind the PGR up-regulation in PCa has not yet been elucidated
  • The PGR is, like the glucocorticoid receptor, similar to androgen receptor with 88% sequence homology in the ligand-binding domain
  • progesterone induced expression of androgen receptor-regulated genes could be a potential mechanism contributing to the development of castrate resistant PCa
  • A possibility of different roles by the two PGR isoforms in normal prostate tissue and PCa, as is suggested for the estrogen receptors [13], must also be taken into account
  • Nathan Goodyear on 03 Jun 18
     
    STudy finds that increased Progesterone receptor expression on epithelial and stromal cells is associated with increased clinical failure of therapy.  Several proposed mechanisms: 88% homologous with androgen receptor suggesting cross-stimulation and via progesterone induced increased androgen receptor gene stimulation i.e. epigenetics.
Nathan Goodyear

Inflammation in Polycystic Ovary Syndrome: underpin... [Steroids. 2012] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...22178787

PCOS inflammation TNF-alpha androgens women polycystic ovarian syndrome

shared by Nathan Goodyear on 05 Nov 12 - No Cached
  • Nathan Goodyear on 05 Nov 12
     
    In women with PCOS, inflammation DIRECTLY stimulates androgen production from the ovaries.  Inflammation is the driving force behind the high androgen levels in women with PCOS.
Nathan Goodyear

Testosterone: a vascular hormone in health and disease - 0 views

joe.endocrinology-journals.org/...R47.full

testosterone hormone health disease hormones men male cardiovascular disease CVD

shared by Nathan Goodyear on 13 May 13 - No Cached
  • Testosterone has beneficial effects on several cardiovascular risk factors, which include cholesterol, endothelial dysfunction and inflammation
  • In clinical studies, acute and chronic testosterone administration increases coronary artery diameter and flow, improves cardiac ischaemia and symptoms in men with chronic stable angina and reduces peripheral vascular resistance in chronic heart failure.
  • testosterone is an L-calcium channel blocker and induces potassium channel activation in vascular smooth muscle cells
  • ...54 more annotations...
  • Animal studies have consistently demonstrated that testosterone is atheroprotective, whereas testosterone deficiency promotes the early stages of atherogenesis
  • there is no compelling evidence that testosterone replacement to levels within the normal healthy range contributes adversely to the pathogenesis of CVD (Carson & Rosano 2011) or prostate cancer (Morgentaler & Schulman 2009)
  • bidirectional effect between decreased testosterone concentrations and disease pathology exists as concomitant cardiovascular risk factors (including inflammation, obesity and insulin resistance) are known to reduce testosterone levels and that testosterone confers beneficial effects on these cardiovascular risk factors
  • Achieving a normal physiological testosterone concentration through the administration of testosterone replacement therapy (TRT) has been shown to improve risk factors for atherosclerosis including reducing central adiposity and insulin resistance and improving lipid profiles (in particular, lowering cholesterol), clotting and inflammatory profiles and vascular function
  • It is well known that impaired erectile function and CVD are closely related in that ED can be the first clinical manifestation of atherosclerosis often preceding a cardiovascular event by 3–5 years
  • no decrease in the response (i.e. no tachyphylaxis) of testosterone and that patient benefit persists in the long term.
  • free testosterone levels within the physiological range, has been shown to result in a marked increase in both flow- and nitroglycerin-mediated brachial artery vasodilation in men with CAD
  • Clinical studies, however, have revealed either small reductions of 2–3 mm in diastolic pressure or no significant effects when testosterone is replaced within normal physiological limits in humans
  • Endothelium-independent mechanisms of testosterone are considered to occur primarily via the inhibition of voltage-operated Ca2+ channels (VOCCs) and/or activation of K+ channels (KCs) on smooth muscle cells (SMCs)
  • Testosterone shares the same molecular binding site as nifedipine
  • Testosterone increases the expression of endothelial nitric oxide synthase (eNOS) and enhances nitric oxide (NO) production
  • Testosterone also inhibited the Ca2+ influx response to PGF2α
  • one of the major actions of testosterone is on NO and its signalling pathways
  • In addition to direct effects on NOS expression, testosterone may also affect phosphodiesterase type 5 (PDE5 (PDE5A)) gene expression, an enzyme controlling the degradation of cGMP, which acts as a vasodilatory second messenger
  • the significance of the action of testosterone on VSMC apoptosis and proliferation in atherosclerosis is difficult to delineate and may be dependent upon the stage of plaque development
  • Several human studies have shown that carotid IMT (CIMT) and aortic calcification negatively correlate with serum testosterone
  • t long-term testosterone treatment reduced CIMT in men with low testosterone levels and angina
  • neither intracellular nor membrane-associated ARs are required for the rapid vasodilator effect
  • acute responses appear to be AR independent, long-term AR-mediated effects on the vasculature have also been described, primarily in the context of vascular tone regulation via the modulation of gene transcription
  • Testosterone and DHT increased the expression of eNOS in HUVECs
  • oestrogens have been shown to activate eNOS and stimulate NO production in an ERα-dependent manner
  • Several studies, however, have demonstrated that the vasodilatory actions of testosterone are not reduced by aromatase inhibition
  • non-aromatisable DHT elicited similar vasodilation to testosterone treatment in arterial smooth muscle
  • increased endothelial NOS (eNOS) expression and phosphorylation were observed in testosterone- and DHT-treated human umbilical vein endothelial cells
  • Androgen deprivation leads to a reduction in neuronal NOS expression associated with a decrease of intracavernosal pressure in penile arteries during erection, an effect that is promptly reversed by androgen replacement therapy
  • Observational evidence suggests that several pro-inflammatory cytokines (including interleukin 1β (IL1β), IL6, tumour necrosis factor α (TNFα), and highly sensitive CRP) and serum testosterone levels are inversely associated in patients with CAD, T2DM and/or hypogonadism
  • patients with the highest IL1β concentrations had lower endogenous testosterone levels
  • TRT has been reported to significantly reduce TNFα and elevate the circulating anti-inflammatory IL10 in hypogonadal men with CVD
  • testosterone treatment to normalise levels in hypogonadal men with the MetS resulted in a significant reduction in the circulating CRP, IL1β and TNFα, with a trend towards lower IL6 compared with placebo
  • parenteral testosterone undecanoate, CRP decreased significantly in hypogonadal elderly men
  • Higher levels of serum adiponectin have been shown to lower cardiovascular risk
  • Research suggests that the expression of VCAM-1, as induced by pro-inflammatory cytokines such as TNFα or interferon γ (IFNγ (IFNG)) in endothelial cells, can be attenuated by treatment with testosterone
  • Testosterone also inhibits the production of pro-inflammatory cytokines such as IL6, IL1β and TNFα in a range of cell types including human endothelial cells
  • decreased inflammatory response to TNFα and lipopolysaccharide (LPS) in human endothelial cells when treated with DHT
  • The key to unravelling the link between testosterone and its role in atherosclerosis may lay in the understanding of testosterone signalling and the cross-talk between receptors and intracellular events that result in pro- and/or anti-inflammatory actions in athero-sensitive cells.
  • testosterone functions through the AR to modulate adhesion molecule expression
  • pre-treatment with DHT reduced the cytokine-stimulated inflammatory response
  • DHT inhibited NFκB activation
  • DHT could inhibit an LPS-induced upregulation of MCP1
  • Both NFκB and AR act at the transcriptional level and have been experimentally found to be antagonistic to each other
  • As the AR and NFκB are mutual antagonists, their interaction and influence on functions can be bidirectional, with inflammatory agents that activate NFκB interfering with normal androgen signalling as well as the AR interrupting NFκB inflammatory transcription
  • prolonged exposure of vascular cells to the inflammatory activation of NFκB associated with atherosclerosis may reduce or alter any potentially protective effects of testosterone
  • DHT and IFNγ also modulate each other's signalling through interaction at the transcriptional level, suggesting that androgens down-regulate IFN-induced genes
  • (Simoncini et al. 2000a,b). Norata et al. (2010) suggest that part of the testosterone-mediated atheroprotective effects could depend on ER activation mediated by the testosterone/DHT 3β-derivative, 3β-Adiol
  • TNFα-induced induction of ICAM-1, VCAM-1 and E-selectin as well as MCP1 and IL6 was significantly reduced by a pre-incubation with 3β-Adiol in HUVECs
  • 3β-Adiol also reduced LPS-induced gene expression of IL6, TNFα, cyclooxygenase 2 (COX2 (PTGS2)), CD40, CX3CR1, plasminogen activator inhibitor-1, MMP9, resistin, pentraxin-3 and MCP1 in the monocytic cell line U937 (Norata et al. 2010)
  • This study suggests that testosterone metabolites, other than those generated through aromatisation, could exert anti-inflammatory effects that are mediated by ER activation.
  • The authors suggest that DHT differentially effects COX2 levels under physiological and pathophysiological conditions in human coronary artery smooth muscle cells and via AR-dependent and -independent mechanisms influenced by the physiological state of the cell
  • There are, however, a number of systematic meta-analyses of clinical trials of TRT that have not demonstrated an increased risk of adverse cardiovascular events or mortality
  • The TOM trial, which was designed to investigate the effect of TRT on frailty in elderly men, was terminated prematurely as a result of an increased incidence of cardiovascular-related events after 6 months in the treatment arm
  • trials of TRT in men with either chronic stable angina or chronic cardiac failure have also found no increase in either cardiovascular events or mortality in studies up to 12 months
  • Evidence may therefore suggest that low testosterone levels and testosterone levels above the normal range have an adverse effect on CVD, whereas testosterone levels titrated to within the mid- to upper-normal range have at least a neutral effect or, taking into account the knowledge of the beneficial effects of testosterone on a series of cardiovascular risk factors, there may possibly be a cardioprotective action
  • The effect of testosterone on human vascular function is a complex issue and may be dependent upon the underlying androgen and/or disease status.
  • the majority of studies suggest that testosterone may display both acute and chronic vasodilatory effects upon various vascular beds at both physiological and supraphysiological concentrations and via endothelium-dependent and -independent mechanisms
  • Nathan Goodyear on 13 May 13
     
    Good deep look into the testosterone and CVD link.
Nathan Goodyear

Testosterone relaxes coronary arteries by opening the large-conductance, calcium-activa... - 0 views

ajpheart.physiology.org/...H1720.full

testosterone vasodilation DHT androgens calcium channels potassium channels

shared by Nathan Goodyear on 14 May 13 - No Cached
  • Nathan Goodyear on 14 May 13
     
    The androgens testosterone and DHT elicit vasodilation via calcium and potassium channel activation.  The vasodilatory effect of the androgens is through, in part, due to K activated Ca channels.  Also of note, DHT had the same effect and DHT cannot be aromatized to estrogen.
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