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Nathan Goodyear

Polysaccharides from Cordyceps sinensis mycelium ... [Pharm Biol. 2014] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...24047103

Cordyceps Cordyceps sinensis exercise performance oxidative stress

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  • Nathan Goodyear on 27 Jan 14
     
    Mouse model finds that Cordyceps increased the interval to exhaustive exercise induced oxidative stress.  SOD, Cat, and GPx were increased in the low, intermediate, and high dose Cordyceps groups.  Oxidative stress markers MDA and 8-OHdG were lower in all groups
Nathan Goodyear

Effect of Cordyceps militaris supplementation ... [Am J Chin Med. 2008] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...19051352

Cordyceps Cordyceps sinensis Testosterone Estradiol sperm

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  • Nathan Goodyear on 27 Jan 14
     
    Cordyceps increased Testosterone, Estradiol, sperm count and motility in mouse model.
Nathan Goodyear

In vivo and in vitro stimulatory effects of Cordyce... [Life Sci. 2003] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...12899935

Cordyceps Cordyceps sinensis Testosterone

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  • Nathan Goodyear on 27 Jan 14
     
    Cordyceps increased Testosterone production in mouse model.
Nathan Goodyear

Cordyceps sinensis promotes exercise endurance capacity of rats by activating skeletal ... - 0 views

www.sciencedirect.com/...S0378874111002923

Cordyceps Cordyceps sinensis exercise performance endurance

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  • Nathan Goodyear on 27 Jan 14
     
    mouse model finds cordyceps improves exercise endurance.  This has, largely, not translated to human studies, though very few studies are available.  
Nathan Goodyear

Cordyceps Sinensis (CordyMax Cs... [Int J Sport Nutr Exerc Metab. 2004] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...15118196

Cordyceps Cordyceps sinensis performance exercise

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  • Nathan Goodyear on 27 Jan 14
     
    Study finds no improvement in performance with Cordyceps over 5 weeks of treatment.  This study looked at endurance performance via VO2 max.
Nathan Goodyear

Effect of Cs-4® (Cordyceps sinensis) on Exercise Performance in Healthy Older... - 0 views

www.ncbi.nlm.nih.gov/...PMC3110835

Cordyceps Cordyceps sinensis exercise performance

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  • Nathan Goodyear on 27 Jan 14
     
    Cordyceps improved lactate threshold and improved exercise performance in healthy, older people.  The dosing was 333mg TID.
Nathan Goodyear

Testosterone responses to intensive inte... [J Endocrinol Invest. 2012] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...23310924

exercise high intensity training HIT hormone hormones Testosterone free 3-alpha androstanediol

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  • Nathan Goodyear on 27 Jan 14
     
    high intensity interval training versus steady state provides different results in post exercise FT.
Nathan Goodyear

The 4-Pregnene and 5α-Pregnane Progesterone Metabolites Formed in Nontumorous... - 0 views

cancerres.aacrjournals.org/...936.full

progesterone metabolism cancer risk 4-pregnene 5alpha-pregnane

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  • We report here the first evidence that tumorous breast tissue exhibits elevated 5α-reductase activity, which promotes significant increases in 5α-pregnanes, especially 5αP,4 whereas the normal (nontumorous) breast tissue produces more 4-pregnenes, especially 3αHP
  • 3αHP and other 4-pregnenes inhibit, whereas 5αP and other 5α-pregnanes stimulate, breast cell proliferation and detachment
  • it is evident that breast tissue can convert progesterone into two classes of metabolites: the δ-4-pregnenes (which retain the C4–5 double bond), and the 5α-reduced 21-carbon steroids (5α-pregnanes)
  • ...12 more annotations...
  • irreversible action of 5α-reductase
  • in normal (nontumorous) breast tissue, the 4-pregnene metabolites of progesterone greatly exceeded the 5α-pregnanes, whereas in tumorous tissue, 5α-pregnanes exceeded 4-pregnenes.
  • These differences in 5α-pregnane and 4-pregnene amounts were largely attributable to differences in 5αP and 3αHP production in tumorous and nontumorous tissues
  • the metabolic activities were in general similar, regardless of the age and ER state of the patient or whether she was pre- or postmenopausal.
  • These findings suggest greatly elevated 5α-reductase activity in tumorous, as compared with nontumorous, breast tissue.
  • progesterone metabolites that retain the C-4 double bond (i.e., the 4-pregnenes) exert an antiproliferative effect in the three cell lines that were tested, whereas the 5α-pregnanes stimulate breast cell line proliferation.
  • the degree of mitogenicity would be determined by the ratio of 5α-pregnanes:4-pregnenes. Tissues with a high 4-pregnene:5α-pregnane ratio would maintain a higher degree of normalcy, whereas those with a high 5α-pregnane:4-pregnene ratio would tend toward tumorigenicity
  • The observations that progesterone metabolites affect both ER-positive and ER-negative cells as well as tumorigenic (MCF-7) and nontumorigenic (MCF-10A) cells strengthen the argument that these factors may be endocrinologically relevant for all forms of breast cancer.
  • progesterone metabolites as the active endocrine/paracrine/autocrine factors
  • Estrogen-based therapies elicit responses in only one-third of all breast cancer patients, and most of these show relapse.
  • the metabolic activities were in general similar, regardless of the age and ER state of the patient or whether she was pre- or postmenopausal.
    • Nathan Goodyear
      Nathan Goodyear on 27 Jan 14
       
      Interesting that the effect of progesterone metabolites were found to be independent from ER status, age, and pre/post menopause
  • Nathan Goodyear on 17 Feb 12
     
    Different progesterone metabolites shown to have different tumor effects.  Implications are that, just as estrogen metabolism effects cancer risk, so does progesterone metabolism.
Nathan Goodyear

Studies on the Progesterone Receptor Content and Steroid Metabolism in Normal and Patho... - 0 views

press.endocrine.org/...jcem-48-4-585

progesterone metabolite metabolites 5-alpha pregnenes hormone hormones metabolism women 4-pregnene 5-alpha pregnene 4-pregnenes breast cancer

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  • Nathan Goodyear on 27 Jan 14
     
    One of the first studies to document progesterone metabolites in breast tissue.
Nathan Goodyear

Are serum hormones associated with the risk of prostate cancer? Prospective results fro... - 0 views

www.sciencedirect.com/...S009042950001116X

serum blood hormone hormones massachusetts male aging study MMAS prostate cancer

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  • Nathan Goodyear on 27 Jan 14
     
    No correlation seen between serum hormones and prostate cancer risk.  Serum evaluation of hormones provides little, if any, clinically, relevant information.  The only association was found with a DHT metabolite--androstanediol.
Nathan Goodyear

Intratumoral De Novo Steroid Synthesis Activates Androgen Receptor in Castration Resist... - 0 views

www.ncbi.nlm.nih.gov/...PMC3209585

prostate cancer DHEA androstenedione

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  • Nathan Goodyear on 27 Jan 14
     
    adrenal androgens contribute to ADT resistant prostate cancer as precursors to T and DHT production.
Nathan Goodyear

http://erc.endocrinology-journals.org/content/18/5/R175.full.pdf - 0 views

erc.endocrinology-journals.org/...R175.full.pdf

DHT metabolite metabolites 3-alpha androstanediol 3-beta androstanediol prostate cancer male hormone hormones men

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  • Nathan Goodyear on 27 Jan 14
     
    Good review of intra-tumor androgen synthesis from DHT metabolites.
Nathan Goodyear

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

shared by Nathan Goodyear on 20 Feb 12 - No Cached
  • P metabolites produced within breast tissues might be independently active hormones functioning as cancer-promoting or -inhibiting regulatory agents
  • 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
  • only a fraction of all breast cancer patients respond to this estrogen-based therapy and the response is only temporary
  • ...30 more annotations...
  • P serves as the precursor for the major steroid hormones (androgens, estrogens, corticosteroids) produced by the gonadal and adrenal cortical tissues.
  • 5α-pregnane, 5β-pregnane, and 4-pregnene metabolites of P
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • The 5α-pregnane-to-4-pregnene ratios were 7- to 20-fold higher in the tumorigenic than in the nontumorigenic cell lines
  • 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
  • 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)
  • 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
  • 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
  • 3αHP inhibited whereas 5αP-stimulated proliferation
  • 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
  • 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 (
  • 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.
  • 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.
  • he effects on proliferation and adhesion were not due to P, but due to the 5α-reduced metabolites
  • The studies showed that binding of 5αP or 3αHP occurs in the plasma membrane fractions, but not in the nuclear or cytosolic compartments
  • 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
  • The studies thus provided the first demonstration of the existence of specific P metabolite receptors
  • 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.
  • Estradiol and 5αP resulted in significant dose-dependent increases, whereas 3αHP and 20αHP each resulted in dose-dependent decreases in total ER
  • In combination, estradiol + 5αP or 3αHP + 20αHP resulted in additive increases or decreases respectively in ER numbers.
  • The data suggest that the action of 5αP on breast cancer cells involves modulation of the MAPK signaling pathway
  • current evidence does not appear to support the notion that increased 5α-reductase activity/ expression might significantly alter androgen influences on breast tumor growth.
  • both testosterone and DHT inhibit cell growth more or less to the same extent
  • Note that 5α-reductase reaction is not reversible
  • Nathan Goodyear on 20 Feb 12
     
    Fantastic read on the effects of progesterone metabolism on tumor and cancer growth.  Tumorigenesis is not just about the hormone, hormone balance, but about the metabolism of hormones.  This is why premarin is so carcinogenic: it is primarily metabolized by the 4-OH estrone pathway.
Nathan Goodyear

Estrogen receptor beta in the prostate - 0 views

www.sciencedirect.com/...S0303720702000898

3-beta androstanediol ER-beta ER beta DHT metabolite ER estrogen receptor receptors prostate cancer male hormone hormones men

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  • Nathan Goodyear on 27 Jan 14
     
    ER beta plays an important role in the prostate.  Loss of ER beta expression in the prostate has been shown to promote carcinogenesis.  In addition, 3-beta androstanediol, a DHT metabolite has been shown to signal through ER beta.
Nathan Goodyear

Mechanisms of Estrogen Action - 0 views

physrev.physiology.org/...1535.full

estrogen receptor receptors ER alpha ER-alpha ER beta ER-beta

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  • Nathan Goodyear on 27 Jan 14
     
    good discussion of estrogen receptors and their role of estrogen signaling transmission.This article goes deep into coregulators, corepressors, cofactors, agonists, antagonists...
Nathan Goodyear

The Estrogen Receptor β Subtype: A Novel Mediator of Estrogen Action in Neuro... - 0 views

www.sciencedirect.com/...S0091302298901704

Estrogen receptors receptor ER alpha ER-alpha ER beta ER-beta hormone hormones

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  • Nathan Goodyear on 27 Jan 14
     
    Estrogen receptors are one mechanism of the transmission of the estrogen signal.  The signal can be from estrogens themselves, estrogenic like compounds (xenoestrogens) and via non-estrogens like 3-beta androstane idol that interacts with ER beta to decrease prostate cancer cell proliferation.
Nathan Goodyear

Comparison of the ligand binding specificity a... [Endocrinology. 1997] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...9048584

DHT metabolite 3-beta androstanediol ER estrogen receptor

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  • Nathan Goodyear on 27 Jan 14
     
    DHT metabolite 3-beta androstanediol has ER affinity, not AR affinity.
Nathan Goodyear

Aromatase activity in the rat brain: Hormonal regulation and sex differences - 0 views

www.sciencedirect.com/...096007609390254T

DHT estradiol Testosterone aromatase

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  • Nathan Goodyear on 27 Jan 14
     
    Rat study finds balance of DHT and estradiol play important role.  The production of DHT removes Testosterone from the pool to make estradiol through aromatase activity.
Nathan Goodyear

The Androgen Derivative 5α-Androstane-3β,17β-Diol Inhibits Prostate Cancer Ce... - 0 views

cancerres.aacrjournals.org/...5445.full

prostate cancer 3-beta androstanediol DHT metabolite E-cadherin ER beta ER-beta male hormone hormones men

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  • In the early stages, prostate cancer growth is dependent on circulating androgens
    • Nathan Goodyear
      Nathan Goodyear on 27 Jan 14
       
      This is in contrast to studies that show poor prognosis with Lower T at time of diagnosis of prostate cancer
  • 5α-reductase not only provides a potent amplification of the androgenic signal ( 4– 6), but it also prevents estrogen formation by subtracting testosterone from the action of aromatase ( 7, 8), thus blocking activation of the estrogen receptor subtypes (ERα and ERβ; refs. 9, 10)
  • ERβ is the prevailing subtype ( 11), and a growing body of evidence points to the protective role of this receptor in prostate cancer
  • ...3 more annotations...
  • It has been shown that the transformation of the dihydrotestosterone to 5α-androstane-3α,17β-diol (3α-diol) and 5α-androstane-3β,17β-diol (3β-Adiol), generates two metabolites unable to bind the androgen receptor, but possessing a very high affinity for the estrogen receptors
  • the effects of testosterone may result from the balance between the androgenic and the estrogenic molecules originating from its catabolism.
  • Recent data have been published postulating a direct estrogenic role of the 3β-hydroxylated derivatives of dihydrotestosterone in the prostate development and homeostasis
  • Nathan Goodyear on 27 Jan 14
     
    Here is the full article.
Nathan Goodyear

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

shared by Nathan Goodyear on 27 Jan 14 - No Cached
  • 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
  • estradiol is not active
  • 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
  • Nathan Goodyear on 27 Jan 14
     
    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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