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Nathan Goodyear

Estrogen receptor β and the progression of prostate cancer: role of 5α-androstane-3β,17β-diol - 0 views

erc.endocrinology-journals.org/...731.long

3-beta androstanediol DHT Testosterone androgens prostate cancer ER beta ER-beta receptors ER men male hormone hormones

shared by Nathan Goodyear on 21 Jan 14 - No Cached
  • In the prostate, ERβ is highly expressed in the epithelial compartment, where it is the prevailing isoform
  • In the gland, DHT may be either reversibly 3α- or irreversibly 3β-hydroxylated by the different 3α- and 3β-hydroxysteroid dehydrogenases respectively (Steckelbroeck et al. 2004); these transformations generate two metabolites respectively 3α-diol and 3β-Adiol, which are both unable to bind the AR. Instead, 3β-Adiol displays a high affinity for ERβ (Kuiper et al. 1998, Nilsson et al. 2001), and it has been proposed that this metabolite may play a key role in prostate development
  • ERβ signaling, in contrast to ERα, seems to act as a suppressor of prostate growth, and may be positively involved in breast cancer
  • ...4 more annotations...
  • 3β-Adiol counteracts PC cell proliferation in vitro
  • 3β-Adiol counteracts the biological actions of its androgenic precursors testosterone and DHT
  • functional antagonism of 3β-Adiol appears to be molecularly independent from the activation of the androgenic pathway
  • the action of 3β-Adiol is mediated, at the molecular levels, by the estrogenic pathway.
  • Nathan Goodyear on 21 Jan 14
     
    another awesome article dealing with hormone metabolites. Physicians that don't understand metabolites and receptors may be doing more harm than good.   One of the mainstays of the treatment of metastatic prostate disease is androgen deprivation therapy.  This article requires a reassessment of this due to the DHT metabolite 3-beta androstanediol.  This metabolite is produced from DHT production via the enzyme 3beta HSD.  This metabolite binds to ER beta, an estrogen receptor, and inhibits proliferation, migration, promotes adhesion (limits spreading), and stimulates apoptosis.  This is contrast to 3-alpha androstanediol.  Androgen deprivation therapy will decrease 3-beta androstanediol.  This is the likely reason for the increased aggressive prostate cancer found in those men using 5 alpha reductase inhibitors.
Nathan Goodyear

The 4-Pregnene and 5α-Pregnane Progesterone Metabolites Formed in Nontumorous and Tumorous Breast Tissue Have Opposite Effects on Breast Cell Proliferation and Adhesion - 0 views

cancerres.aacrjournals.org/...936.long

progesterone metabolite metabolites hormone hormones 5-alpha pregnene 5-alpha pregnenes 3-alpha pregnene 3-alpha pregnenes breast cancer

shared by Nathan Goodyear on 28 Jan 14 - No Cached
  • Nathan Goodyear on 28 Jan 14
     
    Good discussion of the different effects of progesterone metabolites in breast cancer cell lines (in vitro).  This article focused on the biochemical balance of 5alpha pregnane: 3alpha HP.  The increase in this ration promoted proliferation and metastasis, where a decreased ratio did the opposite
Nathan Goodyear

ERβ Has Nongenomic Action in Caveolae: Molecular Endocrinology: Vol 16, No 5 - 0 views

press.endocrine.org/...mend.16.5.0827

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

shared by Nathan Goodyear on 09 Jun 14 - No Cached
  • Nathan Goodyear on 09 Jun 14
     
    Estrogen receptors are primarily located inside the nucleus and in the cytoplasm; not on the cell membrane surface. This article specifically focus' on the non-genomic action of ER-beta.  ER-alpha and ER-beta are classic transcription factors.
Nathan Goodyear

Type 1 5'-deiodinase activity is inhibited by oxidative stress and restored by alpha-lipoic acid in HepG2 cells. - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...26947333

thyroid T3 oxidative stress alpha lipoic acid deiodinase rT3 reverse T3 thyroid metabolites thyroid metabolism hormones

shared by Nathan Goodyear on 28 Sep 16 - No Cached
  • Nathan Goodyear on 28 Sep 16
     
    oxidative stress decreased type 1 deiodinase activity and thus T4 to T3 conversion, resulting in increased rT3 production.  Of interesting note, Alpha lipoic acid increased type I deiodinase activity and T4 to T3 conversion.
Nathan Goodyear

Estrogen Receptor β in Prostate Cancer: Brake Pedal or Accelerator? - 0 views

ajp.amjpathol.org/...fulltext

prostate cancer ER beta ER-beta ER alpha ER-alpha estrogen receptor receptors men male hormone hormones

shared by Nathan Goodyear on 21 Jan 14 - No Cached
  • Nathan Goodyear on 21 Jan 14
     
    Great article on ER beta and the prostate.  ER alpha expression is very important in the development of the prostate.  IN that instance, ER beta is down regulated.  In prostate cancer generation, ER beta expression in the epithelium is lost.
Nathan Goodyear

An endocrine pathway in the prostate, ERβ, AR, 5α-androstane-3β,17β-diol, and CYP7B1, regulates prostate growth - 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

Estradiol-induced proliferation of papillary and follicular thyroid cancer cells is mediated by estrogen receptors α and β - 0 views

www.spandidos-publications.com/...1067

thyroid papillary follicular cancer estrogen estradiol hormone hormones ER alpha ER-alpha ER beta ER-beta PR receptors progesterone

shared by Nathan Goodyear on 25 Nov 13 - No Cached
  • Nathan Goodyear on 25 Nov 13
     
    Estradiol increased thyroid papillary and follicular cancer cells via both ER alpha and ER beta in this study.  What is also interesting is that estradiol did not increase PR expression.
Nathan Goodyear

Pharmacological approaches to reducing the risk of... [Eur Urol. 2009] - PubMed result - 0 views

www.ncbi.nlm.nih.gov/...19200641

finasteride 5 alpha-reductase inhibitors prostate cancer

shared by Nathan Goodyear on 02 Mar 11 - No Cached
  • 5alpha-reductase inhibitors (5-ARIs).
  • there is no evidence that 5-ARIs or any other approach to prostate cancer risk reduction will reduce the risk of lethal prostate cancers
  • Nathan Goodyear on 02 Mar 11
     
    5 alpha-reductase inhibitors, such as finasteride, have not been shown to reduce lethal prostate cancer
Nathan Goodyear

Altered Cortisol Metabolism in Polycystic Ovary Syndrome: Insulin Enhances 5α-Reduction But Not the Elevated Adrenal Steroid Production Rates - 0 views

jcem.endojournals.org/...5907.long

PCOS PCO polycystic ovaries insulin IR resistance steroid 5-alpha reductase androgens

shared by Nathan Goodyear on 13 Mar 12 - No Cached
  • Nathan Goodyear on 13 Mar 12
     
    insulin, in women with PCOS, promotes increased 5-alpha reductase activity.  This results in a dysregulated HPA axis, promoting increased cortisol and androgen levels.
Nathan Goodyear

Increased 5α-Reductase Activity and Adrenocortical Drive in Women with Polycystic Ovary Syndrome - 0 views

jcem.endojournals.org/...3558.long

5-alpha reductase activity women PCOS PCO polycystic ovary ovarian syndrome 11-betaHSD

shared by Nathan Goodyear on 13 Mar 12 - No Cached
  • Nathan Goodyear on 13 Mar 12
     
    increased 5-alpha reductase activity found in women with PCOS. Weight showed no variance.  Additionally, no change in 11-betaHSD activity was found.
Nathan Goodyear

Activity and expression of progesterone metabolizing 5α-reductase, 20α-hydroxysteroid oxidoreductase and 3α(β)-hydroxysteroid oxidoreductases in tumorigenic (MCF7, MDA-MB-231, T-47D) and nontumorigenic (MCF10A) human breast cancer cells - ResearchGate - 0 views

www.researchgate.net/...10A)_human_breast_cancer_cells

progesterone metabolites breast cancer 5-alpha-pregnanediol 4-pregnenediol

shared by Nathan Goodyear on 23 Jan 14 - No Cached
  • Nathan Goodyear on 23 Jan 14
     
    Intra mammary progesterone metabolism and its associated metabolites found to be associated with tumorigenic activity in cell lines.  This was independent from ER PR status.  5 alpha-pregnanes were found to be pro-tumor and 4-pregnanes were anti-tumor.
Nathan Goodyear

5α-reductase type 3 enzyme in benign and malignant ... [Prostate. 2014] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...24150795

5 alpha reductase prostate cancer

shared by Nathan Goodyear on 06 Feb 14 - No Cached
  • Nathan Goodyear on 06 Feb 14
     
    3 subtypes of 5 alpha reductase enzymes identified in the human prostate.
Nathan Goodyear

Testosterone replacement in prostate cancer survivors with hypogonadal symptoms - Leibowitz - 2009 - BJU International - Wiley Online Library - 0 views

onlinelibrary.wiley.com/...full

testosterone replacement prostate cancer PSA 5-alpha reductase inhibitor

shared by Nathan Goodyear on 25 Sep 13 - No Cached
  • Nathan Goodyear on 25 Sep 13
     
    Good article.  This article (case series) found that 40% of the men included had no increase in PSA with Testosterone.  One point on the Testosterone dosage is that they used androgen, which is an overdose of Testosterone.  That gives 60% that the PSA did increase.  These men had higher PSA to begin with which leads to the suggestion that the prostate cells were abnormal.  Those men that had a prostatectomy were more likely to have little if any increase in PSA.  This study did use a the 5 alpha reductase inhibitor dutasteride.
Nathan Goodyear

Altered Cortisol Metabolism in Polycystic Ovary Syndrome: Insulin Enhances 5α-Reduction But Not the Elevated Adrenal Steroid Production Rates - 0 views

jcem.endojournals.org/...5907.short

PCOS women lean 11-betaHSD1 5-alpha-reductase androgens testosterone insulin syndrome

shared by Nathan Goodyear on 25 Apr 12 - No Cached
  • Nathan Goodyear on 25 Apr 12
     
    lean women with PCOS found to have reduced 11 beta-HSD1 and increased 5 alpha reductase activity.  This, in part, is associated with the elevated cortisol and androgens in these women.
Nathan Goodyear

Body Fat Distribution and Cortisol Metabolism in Healthy Men: Enhanced 5β-Reductase and Lower Cortisol/Cortisone Metabolite Ratios in Men with Fatty Liver - 0 views

jcem.endojournals.org/...4924.long

cortisone cortisol obesity overweight men 11-betaHSD type 1 5-alpha reductase metabolism

shared by Nathan Goodyear on 13 Mar 12 - No Cached
  • Nathan Goodyear on 13 Mar 12
     
    increased 11-betaHSD type 1 and increased 5-alpha reductase activity found to be associated with generalized obesity in men.  Both indicate increased cortisone to cortisol production.  
Nathan Goodyear

Progesterone metabolites regulate induction, growth, and suppression of estrogen- and progesterone receptor-negative human breast cell tumors - 0 views

www.ncbi.nlm.nih.gov/...PMC3706910

progesterone metabolites metabolite 5-alpha pregnene 5-alpha pregnenes 5alpha-dihydroprogesterone 4-pregnene 4-pregnenes 3alpha-dihydroprogesterone breast cancer ER PR hormone hormones receptors estrogen

shared by Nathan Goodyear on 28 Jan 14 - No Cached
  • in vitro studies had shown that the progesterone metabolites, 5α-dihydroprogesterone (5αP) and 3α-dihydroprogesterone (3αHP), respectively, exhibit procancer and anticancer effects on receptor-negative human breast cell lines
  • Onset and growth of ER/PR-negative human breast cell tumors were significantly stimulated by 5αP and inhibited by 3αHP
  • When both hormones were applied simultaneously, the stimulatory effects of 5αP were abrogated by the inhibitory effects of 3αHP and vice versa
  • ...31 more annotations...
  • Treatment with 3αHP subsequent to 5αP-induced tumor initiation resulted in suppression of further tumorigenesis and regression of existing tumors
  • Tumorigenesis of ER/PR-negative breast cells is significantly enhanced by 5αP and suppressed by 3αHP, the outcome depending on the relative concentrations of these two hormones in the microenvironment in the breast regions
  • The findings show that the production of 5αP greatly exceeds that of 3αHP in ER/PR-negative tumors and that treatment with 3αHP can effectively block tumorigenesis and cause existing tumors to regress
  • hypothesis that a high 3αHP-to-5αP concentration ratio in the microenvironment may foster normalcy in noncancerous breast regions.
  • a large proportion (about 30% to 60%) of breast tumors are ER and/or PR negative
  • about 90% of normal proliferating breast epithelial cells are receptor negative
  • Our previous in vitro studies had shown that breast tissues and cell lines readily convert progesterone to 5α-pregnanes, such as 5αP, and delta-4-pregnenes, such as 3αHP (Figure ​(Figure1),1), and that tumorous breast tissues [15] and tumorigenic breast cell lines [16] produce higher levels of 5αP and lower levels of 3αHP than do normal breast tissues and nontumorigenic cell lines
  • The progesterone metabolism studies suggested that increases in 5αP and decreases in 3αHP production accompany the shift toward breast cell neoplasia and tumorigenicity
  • In vitro studies on five different human breast cell lines showed that cell proliferation and detachment are significantly increased by 5αP and decreased by 3αHP
  • the prevailing theory of hormonal regulation of breast cancer, as well as hormone-based therapies, revolves around estrogen and/or progesterone and ER/PR-positive breast cells and tumors.
  • Not only do these "receptor-negative" breast cancers fail to benefit from current hormonal therapies, but they also generally exhibit more-aggressive biologic behaviors and poorer prognosis than the receptor-positive ones
  • The results of the studies reported here show for the first time that the progesterone metabolites, 5αP and 3αHP, act as hormones that regulate ER/PR-negative breast tumor formation, growth, and regression
  • The onset of the ER/PR-negative human breast cell tumors in mice was considerably accelerated, and the growth significantly stimulated, by just one or two applications of 5αP
  • In contrast, 3αHP retarded onset of tumor formation, suppressed tumor growth, and inhibited or regressed existing 5αP-induced tumors
  • When both hormones were administered simultaneously, the effects of one were abrogated by the effects of the other.
  • The 5αPR and 3αHPR (which are associated with the plasma membranes of both ER/PR-positive [19] and ER/PR-negative [29] cells) are distinct from each other and from known ER, PR, androgen, and corticosteroid receptors, and lack affinity for other steroids, such as progesterone, estrogen, androgens, corticosteroids, and other progesterone metabolites
  • Levels of 5αPR are upregulated by 5αP itself and estradiol, and downregulated by 3αHP in both ER/PR-positive and -negative cells
  • ndications are that 5αP acts via the surface receptor-linked mitogen-activated protein kinase (MAPK; Erk1/2) pathway; 5αP significantly stimulates activation of Erk1/2 [30], increases the Bcl-2/Bax expression ratio [18] and actin depolymerization [31], and decreases expression of actin and adhesion plaque-associated vinculin [31], resulting in decreased apoptosis and increased mitosis and cell detachment
  • 3αHP appears to suppress protein kinase C (PKC), phospholipase C (PLC), Ca2+ mobilization (unpublished observations), and the Bcl-2/Bax expression ratio [18], and increases expression of the cell-cycle inhibitor p21 [18], resulting in increased apoptosis and decreased proliferation and detachment of breast cell lines.
  • serum from mice with tumors had significantly more 5αP than 3αHP
  • the tumors, which on average had about threefold higher concentrations of 5αP than the respective sera, and >10-fold higher 5αP than 3αHP levels
  • Previous in vitro metabolism studies showed that human breast tumor tissues convert significantly more progesterone to 5α-pregnanes like 5αP and less to 4-pregnenes like 3αHP than do paired normal (nontumorous) tissues
  • Similar differences in progesterone metabolism and enzyme gene expressions were observed between tumorigenic and nontumorigenic breast cell lines
  • breast carcinomas are able to synthesize progesterone
  • The current findings, along with the previous in vitro studies, suggest that the relative concentrations of 5αP and 3αHP in the breast microenvironment constitute important autocrine/paracrine determinants not only for tumorigenesis but also for potential regression of tumors and the maintenance of normalcy of ER/PR-negative breast cells/tissues.
  • Evidence presented here shows that a high concentration of 5αP, relative to 3αHP in the microenvironment, promotes initiation and growth of tumors, whereas a higher concentration of 3αHP, relative to 5αP, suppresses tumorigenesis and promotes normalcy
  • 5α-reductase and 5αPR levels are upregulated by 5αP
  • in the 3αHP-treated mice, the elevated 3αHP levels, relative to 5αP, in the microenvironment could have opposed progression to xenograft neoplasia by its inherent anticancer actions and the suppression of 5αP synthesis and 5αPR expression
  • the opposing actions of the progesterone metabolites also appear to exert some control over the estrogen-regulated effects on breast cancer by their ability to modulate ER numbers in ER-positive cells
  • because both ER/PR-negative and ER/PR-positive, as well as normal and tumorigenic human breast cell lines, have been shown to respond to 5αP and 3αHP in vitro, it is suggested that these endogenously produced progesterone metabolites may also play regulatory hormonal roles in ER/PR-positive breast cancers, as well as in the maintenance of normalcy in nontumorous breast tissues.
  • The in vivo data provide further evidence that progesterone metabolites, such as 5αP and 3αHP, deserve to be considered as active hormones in their own right, rather than inactive waste products
  • Nathan Goodyear on 28 Jan 14
     
    Progesterone metabolites and breast cancer
Nathan Goodyear

Leydig Cells: Endocrine, Paracrine, and Autocrine Regulation: Endocrine Reviews: Vol 15, No 5 - 0 views

press.endocrine.org/...edrv-15-5-574

inflamation inflammatory cytokines cytokines TNF-alpha leydig cells Testosterone hormone hormones

shared by Nathan Goodyear on 31 Mar 15 - No Cached
  • Nathan Goodyear on 31 Mar 15
     
    Older article here, and only abstract available.  TNF-alpha decreased Leydig Testosterone production.
Nathan Goodyear

Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets: Trends in Pharmacological Sciences - 0 views

www.cell.com/...S0165-6147(08)00252-6

inflammation curcumin NF-kappaB TNF-alpha IL-1 IL-6 disease

shared by Nathan Goodyear on 22 Mar 16 - No Cached
  • Nathan Goodyear on 22 Mar 16
     
    Just abstract available here.  Curcumin reduces NF-kappaB, Cox2 and 5 lipoxygenase and the cytokines TNF-alpha and IL-1 and IL-6.  This implicates curcumin as an adjuvant for all chronic diseases of aging that involve inflammation.
Nathan Goodyear

Omega-3 Fatty Acids and Inflammatory Processes - 0 views

www.ncbi.nlm.nih.gov/...PMC3257651

fats nutrition diet omega 3 inflammation NF-kappaB TNF-alpha omega-3 fish oil DHA EPA docosahexaenoic acid eicosapentaenoic acid

shared by Nathan Goodyear on 15 Sep 17 - No Cached
  • marine n-3 PUFAs have also been shown to alter the production of inflammatory proteins including chemokines, cytokines, growth factors and matrix proteases
  • Two transcription factors that are likely to play a role in inflammation are nuclear factor κ B (NFκB) and PPAR-γ
  • NFκB is the principal transcription factor involved in upregulation of inflammatory cytokine, adhesion molecule and cyclooxygenase-2 genes
  • ...3 more annotations...
  • PPAR-γ, is believed to act in an anti-inflammatory manner
  • PPAR-γ directly regulates inflammatory gene expression, it also interferes with the activation of NFκB creating an intriguing interaction between these two transcription factors
  • Both NFκB and PPAR-γ may be regulated by n-3 PUFAs.
  • Nathan Goodyear on 15 Sep 17
     
    great review of the anti-inflammatory effects of omega 3 DHA and EPA.  EPA inhibits COX and 5-LOX and their downstream prostaglandin and leukotrienes.  EPA/DHA inhibited endotoxin-stimulated IL-6, IL-8,TNF-alpha, and NFkappaB.
Nathan Goodyear

Long-Term Immunomodulatory Effects of a Mediterranean Diet in Adults at High Risk of Cardiovascular Disease in the PREvención con DIeta MEDiterránea (PREDIMED) Randomized Controlled Trial - 0 views

jn.nutrition.org/...1684.short

mediterranean mediterranean diet heart health heart nutrition cardiovascular disease inflammation hsCRP CRP TNF-alpha

shared by Nathan Goodyear on 01 Jun 17 - No Cached
  • Nathan Goodyear on 01 Jun 17
     
    Mediterranean diet found to reduce hsCRP, IL-6, TNF-alpha, and MCP in high-risk adults out to 5 years!  This study compared the Mediterranean diet to a low fat diet.
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