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Nathan Goodyear

Role of Polymorphic Human Cytochrome P450 Enzymes in Estrone Oxidation - 0 views

cebp.aacrjournals.org/...551.long

estrogen metabolism estrogen metabolites cytochrome P450 estrogen estrone hormones detoxification metabolites

shared by Nathan Goodyear on 11 Sep 15 - No Cached
  • CYP1A1 and CYP1B1 are not expressed in any significant quantity in the liver. Therefore, they would not be expected to contribute to the overall systemic metabolism of estrone. However, both enzymes have been identified in breast tissue
  • CYP1A1 displayed relatively high activity for all three hydroxylations, suggesting that it may play an important role in extrahepatic tissues where it is expressed
  • CYP1A1 was more active with regard to 2-hydroxylation and 4-hydroxylation, it also displayed one of the greatest 16α-hydroxylating activities of the CYP enzymes tested.
  • ...4 more annotations...
  • CYP1B1 displayed a high affinity for estrone and preferentially catalyzed 4-hydroxylation over 2-hydroxylation
  • CYP1B1 did not seem to contribute to 16α-hydroxylation.
  • CYP1B1 was shown to preferentially catalyze 4-hydroxylation, whereas CYP1A1 was shown to preferentially catalyze 2-hydroxylation
  • Among the CYP enzymes expressed in the liver, CYP1A2 was the most active with regard to 2-hydroxylation
  • Nathan Goodyear on 11 Sep 15
     
    good discussion of estrogen metabolism and the P450 enzymes.
Nathan Goodyear

An endocrine pathway in the prostate, ERβ, AR, 5α-androstane-3β,17β-diol, and... - 0 views

www.pnas.org/...13589.full

3-beta androstanediol DHT metabolite prostate cancer ER-beta ER beta CYP7b1 cytochrome male hormone hormones men

shared by Nathan Goodyear on 27 Jan 14 - No Cached
  • Although the prostate is an androgen-dependent tissue, estrogens influence both normal functions and pathological changes in this gland
  • This dual action may be due to the existence of two estrogen receptors, ERα and ERβ
  • ERα and ERβ have similar affinities for estradiol-17β
  • ...6 more annotations...
  • In this study we have shown that regulation of the levels of 3βAdiol by CYP7B1 is a key factor in regulation of prostatic growth
  • We provide evidence that proliferating cells in the prostate epithelium have elevated levels of AR and that AR protein but not mRNA levels are regulated by ERβ and its ligand 3βAdiol in the prostate epithelium.
  • because inhibition of 5α-reductase causes accumulation of testosterone and removal of ERβ action increases the level of AR in the prostate, the overall effect of Finasteride would be to favor proliferation of the prostate epithelium
  • studies show that ERβ tends to be lost in advanced prostate cancer.
  • DHEA is converted in the body to 5-androstene-3β,17β-diol, which is also a ligand for estrogen receptors (25, 39) and a substrate for CYP7B1
  • At the peak of proliferation, the proliferating epithelial cells in the ventral prostate expressed high levels of CYP7B1 but had no detectable ERβ, whereas in nonproliferating cells the level of ERβ was high and that of CYP7B1 was low.
  • Nathan Goodyear on 27 Jan 14
     
    3-beta androstanediola, a product of 3alpha-HSD from DHT binds to ER beta and down regulates AR in prostate cancer.  This study proposes that the mechanism is via CYP7B1.  CYP7B1 inactivates 3-beta androstanediol.  Interesting, because 3-beta androstanediol is considered "inactive" when compared to 3-alpha androstanediol and its interaction with ER alpha.  
Nathan Goodyear

Regulation of CYP3A4 and CYP3A5 expressi... [Mol Cell Endocrinol. 2012] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...22939842

VDR vitamin D receptors CYP3A4

shared by Nathan Goodyear on 29 Nov 13 - No Cached
  • Nathan Goodyear on 29 Nov 13
     
    Vitamin D receptors found to increase CYP3A4 and CYP3A5 expression.  This has impacts on hormone metabolism.  According to the results, low vitamin D will result in decreased clearance of hormone through particularily through the CYP3A4 pathway.
Nathan Goodyear

Colonization-Induced Host-Gut Microbial Metabolic Interaction - 0 views

mbio.asm.org/...e00271-10.full

gut flora gut microbiome gut microbiota CYP450 metabolism

shared by Nathan Goodyear on 06 May 15 - No Cached
  • he gut microbiota enhances the host’s metabolic capacity for processing nutrients and drugs and modulate the activities of multiple pathways in a variety of organ systems.
  • Acquisition of the gut microbiota was associated with rapid increase in body weight (4%) over the first 5 days of colonization
  • The colonization process stimulated glycogenesis in the liver prior to triggering increases in hepatic triglyceride synthesis
  • ...11 more annotations...
  • modifications of hepatic Cyp8b1 expression and the subsequent alteration of bile acid metabolites
  • Expression and activity of major drug-metabolizing enzymes (Cyp3a11 and Cyp2c29) were also significantly stimulated
  • The gut microbiota (GM) exhibits a relatively low level of diversity compared to those of most soil ecosystems and in humans it is comprised of usually no more than nine phyla of microorganisms, of which only two are dominant: the Firmicutes and the Bacteroidetes
  • colonization of a germfree gut was rapid and remarkably stable, establishing within only a week after first exposure
  • a study conducted on germfree rats by Nicholls et al. showed that 3 weeks were necessary to obtain a stabilization and “normalization”
  • the microbiota status affects the systemic metabolism of the host, modulating the metabolic fingerprint of topographically remote organs such as the liver and the kidney
  • Gut colonization induces a rapid weight gain associated with stimulation of hepatic glycogenesis and triglyceride synthesis
  • Gut colonization alters bile acid metabolite profiles via modulation of hepatic Cyp8b1 expression
  • Bile acids are well-known contributors to glucose and lipid metabolism in the liver
  • GM is known to alter bile metabolism
  • GM is also known to exert a strong influence on the metabolism of xenobiotics
  • Nathan Goodyear on 06 May 15
     
    The effects of gut microbiome are not confined to the gut.  They alter bile acid metabolism and thus lipid/glucose metabolism.  They alter CYP450 activity.  They effect metabolism.  They effect the metabolism, and thus effects, of other drugs. 
Nathan Goodyear

Selective serotonin reuptake inhibitors - PubMed Mobile - 0 views

www.ncbi.nlm.nih.gov/...11876575

SSRI CYP cytochrome P450 estrogen

shared by Nathan Goodyear on 01 Nov 13 - No Cached
  • Nathan Goodyear on 01 Nov 13
     
    SSRI's have variable inhibition of CYP.  Fluvoxamine was found to be the most potent inhibitor.  CYP3A4 and CYP2D6 were found to be the main targets of inhibition.  
Nathan Goodyear

Cigarette smoking and hormones : Current Opinion in Obstetrics and Gynecology - 0 views

journals.lww.com/...te_smoking_and_hormones.3.aspx

smoking tobacco CYP1A1 CYP1B1 estrogen hormones estrogen metabolism estrogen metabolites

shared by Nathan Goodyear on 05 Dec 16 - No Cached
  • Epidemiologic studies worldwide have established that exposure to cigarette smoke is an important cause of estrogen deficiency.
  • Nathan Goodyear on 05 Dec 16
     
    tobacco smoke alters estrogen metabolism.  Increase in CYP1B1 and CYP1B1 are the result of tobacco smoke.
Nathan Goodyear

Progesterone and testosterone hydroxyla... [Arch Biochem Biophys. 1997] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...9328296

progesterone testosterone cytochrome metabolization detoxification

shared by Nathan Goodyear on 07 Dec 12 - No Cached
  • Nathan Goodyear on 07 Dec 12
     
    Progesterone and testosterone metabolized by CYP2C9 and CYP2C19.
Nathan Goodyear

Iodine Alters Gene Expression in the MCF7 Breast Cancer Cell Line: Evidence for an Anti... - 0 views

www.medsci.org/v05p0189.htm

iodine breast cancer health women

shared by Nathan Goodyear on 15 Nov 11 - No Cached
  • Nathan Goodyear on 15 Nov 11
     
    Iodine shown to elicit anti-estrogenic effect through altering estrogen metabolization through cyp 1A1instead of the cyp 1B1 pathway.  Important implications in the breast health of women.
Nathan Goodyear

Entropy | Free Full-Text | Glyphosate's Suppression of Cytochrome P450 Enzymes and Amin... - 0 views

www.mdpi.com/...1416

glyphosate CYP CYP450 detoxification gut microbiome gut flora gut microbiota

shared by Nathan Goodyear on 30 Apr 15 - No Cached
  • Nathan Goodyear on 30 Apr 15
     
    Glyphosate disrupts CYP450 pathways.
Nathan Goodyear

Cytochrome P450-mediated metabolism of - PubMed Mobile - 0 views

www.ncbi.nlm.nih.gov/...16112414

estrogen metabolism CYP Cytochrome P450 hormones

shared by Nathan Goodyear on 01 Nov 13 - No Cached
  • Nathan Goodyear on 01 Nov 13
     
    Just the abstract here, but a good review of CYP and estrogen metabolism
Nathan Goodyear

Hepatotoxicity of Herbal Supplements Mediated by Modulation of Cytochrome P450 - 0 views

www.ncbi.nlm.nih.gov/...PMC5713322

CYP450 detoxification supplements herbs herbal therapies

shared by Nathan Goodyear on 13 Jan 18 - No Cached
  • Nathan Goodyear on 13 Jan 18
     
    awesome review of herbal supplements and CYP450 interactions
Nathan Goodyear

Monsanto Roundup: The Impacts of Glyphosate Herbicide on Human Health. Pathways to Mode... - 0 views

www.globalresearch.ca/...5342520

monsanto roundup glyphosate

shared by Nathan Goodyear on 12 Aug 13 - No Cached
  • Nathan Goodyear on 12 Aug 13
     
    Glyphosate inhibits CYP 450 enzymes.  The author states it well: "glyphosate enhances the damaging effects fo other food borne chemical residues and environnmental toxins.  Additionally, Glyphosate disrupts gut bacterial function in the human gut. This dysbiosis is well known to cause systemic disease, such as obesity, diabetes...
Nathan Goodyear

Testosterone Levels and Sexual Function Disorders ... [J Sex Med. 2013] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...24286389

testosterone women depression antidepressants

shared by Nathan Goodyear on 02 Dec 13 - No Cached
  • Nathan Goodyear on 02 Dec 13
     
    Interesting finding in this study. They looked at Total Testosterone and bioavailable Testosterone and found that antidepressant therapy increased both values post treatment.  This is counter to what has been readably seen in men--with a decline.  The abstract here does not point disclose the actual Testosterone numbers.  I wonder if the well known disruption of the CYP enzymes by antidepressants slowed clearance and increased Testosterone levels.  This study did not look at other hormones or inflammatory cytokines.  Very tunneled vision study.  Nothing can be drawn from this study.
Nathan Goodyear

CYP1A1 and CYP1B1 polymorphisms and their association with estradiol and estrogen metab... - 0 views

www.ncbi.nlm.nih.gov/...16949388

estrogen metabolites estrogen metabolism menopause estrogen hormones

shared by Nathan Goodyear on 11 Sep 15 - No Cached
  • Nathan Goodyear on 11 Sep 15
     
    estrogen metabolites and associated risk.
Nathan Goodyear

27-Hydroxycholesterol Links Hypercholesterolemia and Breast Cancer Pathophysiology - 0 views

www.sciencemag.org/...1094

breast cancer cholesterol ER estrogen receptor

shared by Nathan Goodyear on 04 Jan 14 - No Cached
  • Nathan Goodyear on 04 Jan 14
     
    Study finds link between cholesterol metabolite and breast cancer.  The interesting point of this article is not that statins need to be given to all women to prevent breast cancer, which of course is what many will take.  But, that the cholesterol metabolite, 27-hydroxycholesterol showed ER agonist activity.  This would have to be ER-alpha agonist activity though the authors did not clarify.  The 27-hydroxymetabolite is created from CYP27A1.
Nathan Goodyear

Endocrinology of the Aging Male - 0 views

www.ncbi.nlm.nih.gov/...PMC3073592

aging male hormone hormones

shared by Nathan Goodyear on 30 Apr 13 - No Cached
  • All steps beyond the formation of pregnenolone take place in the smooth endoplasmic reticulum
  • Cytochrome P450 enzyme, CYP11A is located on the inner mitochondrial membrane and catalyses the rate limiting step of pregnenolone synthesis
  • Estrogen and related steroids, thyroid hormone and insulin increase SHBG levels.
  • ...21 more annotations...
  • SHBG decreases in response to androgens, and in the presence of hypothyroidism, and insulin resistance.
  • Plasma SHBG levels tend to increase with increasing age
  • The apparent metabolic clearance rate of testosterone is decreased in elderly as compared to younger men
  • Testosterone circulates predominantly bound to the plasma proteins SHBG and albumin, with high and low affinity respectively
  • Testosterone is secreted in a pulsatile fashion
  • Current clinical guidelines suggest at least two measurements
  • In adult men, there is a well-documented diurnal variation (particularly in younger subjects) in testosterone levels, which are highest in the early morning and progressively decline throughout the day to a nadir in the evening
  • In older men, the diurnal variation is blunted
  • it is standard practice for samples to be obtained between 0800 and 1100 h.
  • Testosterone and DHEA decline, whereas LH, FSH, and SHBG rise
  • DHT remains constant despite the decline of its precursor testosterone
  • Longitudinal studies show an average annual decline of 1–2% total testosterone levels, with decline in free testosterone more rapid because of increases in SHBG with aging
  • Massachusetts Male Aging Study (MMAS) data show DHEA, DHEAS, and Ae declining at 2–3% per year
  • DHT showed no cross-sectional age trend
  • Androstanediol glucuronide (AAG) declined cross-sectionally with age in the MMAS sample, at 0.6% per year
  • The EMAS data show that, consistent with the longitudinal findings of MMAS (Figure 1), the core hormonal pattern with increasing age is suggestive of incipient primary testicular dysfunction with maintained total testosterone and progressively blunted free testosterone associated with higher LH
    • Nathan Goodyear
      Nathan Goodyear on 01 May 13
       
      This author proves the point in the review of these two studies, that TT may remain constant in aging men, however, FT drops.
  • obesity impairs hypothalamic/pituitary function
  • Androgen deprivation in men with prostate cancer has been associated with increased insulin resistance, worse glycemic control, and a significant increase in risk of incident diabetes
  • Low serum testosterone is associated with the development of metabolic syndrome 116, 117 and type 2 diabetes. 118 SHBG has been inversely correlated with type 2 diabetes
  • Improvement in insulin sensitivity with testosterone treatment has been reported in healthy 121 and diabetic 122 adult men
  • In studies conducted in men with central adiposity, testosterone has been shown to inhibit lipoprotein lipase activity in abdominal adipose tissue leading to decreased triglyceride uptake in central fat depots. 123
  • Nathan Goodyear on 30 Apr 13
     
    great review of hormone changes associated with aging in men.
Nathan Goodyear

Thyroid Hormones Decrease Plasma 1α,25-Dihydroxyvitamin D Levels Through Tran... - 0 views

endo.endojournals.org/...609.abstract

thyroid hormone hormones T3 vitamin D

shared by Nathan Goodyear on 13 Feb 13 - No Cached
  • Nathan Goodyear on 13 Feb 13
     
    T3 can suppress kidney production of 1 alpha,25-dihyddroxyvitamin D.
Nathan Goodyear

Efficacy of Artichoke dry extract in patients with hyperlipoproteinemia. - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...10758778

artichoke artichoke extract natural alternative CYP450 cholesterol LDL atherosclerosis coronary heart disease

shared by Nathan Goodyear on 06 Jul 16 - No Cached
  • Nathan Goodyear on 06 Jul 16
     
    artichoke extract found to be beneficial in treating hypoerlipoproteinamia.
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