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Nathan Goodyear

Estrogen receptor β and the progression of prostate cancer: role of 5α-andros... - 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

Progesterone metabolites regulate induction, growth, and suppression of estrogen- and p... - 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

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

Intratumoral androgen biosynthesis in prostate cancer pathogenesis and response to therapy - 0 views

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

prostate cancer DHT 3-beta-diol 3-alpha-diol metabolites metabolite male men hormone hormones androgen deprivation therapy

shared by Nathan Goodyear on 03 Feb 14 - No Cached
  • Additional studies have similarly found that prostate tissue levels of DHT in PCa patients treated with ADT therapy before prostatectomy declined by only ∼75% versus declines of ∼95% in serum levels
  • In a recent study in healthy men, treatment for 1 month with a GnRH antagonist to suppress testicular androgen synthesis caused a 94% decline in serum testosterone, but only a 70–80% decline in prostate tissue testosterone and DHT
  • progression to CRPC was associated with increased intratumoral accumulation or synthesis of testosterone.
  • ...9 more annotations...
  • the intraprostatic synthesis of testosterone from adrenal-derived precursors likely accounts for the relatively high testosterone levels in prostate after ADT
  • In addition, AR activity in these cells is likely further enhanced by multiple mechanisms that sensitize AR to low levels of androgens
  • higher affinity ligand DHT (approximately eightfold higher affinity
  • type 2 5α-reductase (SRD5A2) being the major enzyme in prostate
  • reduce DHT to 5α-androstane-3α,17β-diol (3α-androstanediol; Ji et al. 2003, Rizner et al. 2003), which is then glucuronidated to form 3α-androstanediol glucuronide by the enzymes UDP glycosyltransferase 2, B15 (UGT2B15) or UGT2B17
  • DHT in prostate is inactivated by the enzyme AKR1C2, which is also termed 3α-hydroxysteroid dehydrogenase type 3 (3α-HSD type 3
    • Nathan Goodyear
      Nathan Goodyear on 03 Feb 14
       
      The metabolite 3-alpha androstanediol is NOT inactive as this author states.  This DHT metabolite actually can stimulate  ER alpha receptors in the prostate.
  • AKR1C1, is also expressed in prostate. However, in contrast to AKR1C2, it converts DHT primarily to 5α-androstane-3β,17β-diol (3β-androstanediol; Steckelbroeck et al. 2004), which is a potential endogenous ligand for the estrogen receptor β
  • Significantly, intraprostatic testosterone levels were not substantially reduced relative to controls with normal serum androgen levels, although DHT levels were reduced to 18% of controls
  • testosterone levels in many of the CRPC samples were actually increased relative to control tissues (Montgomery et al. 2008). While DHT levels were less markedly increased, this may have reflected DHT catabolism
  • Nathan Goodyear on 03 Feb 14
     
    This article discusses the failure of androgen deprivation therapy and prostate cancer.  This failure is quite common.  The authors point to alpha-DHT as the primary mechanism through AR stimulation.  However, we know that DHT metabolites also stimulate estrogen receptors.
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

Potential Prostate Cancer Drug Target: Bioactivation of Androstanediol by Conversion to... - 0 views

clincancerres.aacrjournals.org/...5844.full

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

shared by Nathan Goodyear on 03 Feb 14 - No Cached
  • Nathan Goodyear on 03 Feb 14
     
    Article discusses the the conversion of 3-alpha-diol back to DHT and this role in prostate cancer in androgen deprivation therapy.  What we now know is that this metabolite interacts with ER alpha receptor to promote proliferation.  Carcinogenesis appears to be primarily an estrogen driven process and her in prostate cancer, the androgen metabolites are promoting proliferation through estrogen receptors.
Nathan Goodyear

The Androgen 5α-Dihydrotestosterone and Its Metabolite 5α-Androstan-3β, 17β-D... - 0 views

www.jneurosci.org/...1448.full

DHT 3 beta androstanediol androgens Hypothalamus HPA hormones stress

shared by Nathan Goodyear on 15 Jul 15 - No Cached
  • Sex steroid hormones are primarily responsible for sex difference in adult HPA function; androgens inhibit whereas estrogens enhance HPA axis activation after a stressor
  • the PVN contains relatively high levels of AR (Bingaman et al., 1994; Zhou et al., 1994) and ERβ (Alves et al., 1998; Hrabovszky et al., 1998; Somponpun and Sladek, 2003) but is essentially devoid of ERα
  • the nonaromatizable androgen DHT and the nonselective ER ligand E2 influence HPA reactivity by acting on neurons within or surrounding the PVN
  • ...9 more annotations...
  • inhibitory action of DHT is detectable at both the level of hormone secretion as well as PVN c-fos mRNA expression
  • the inhibition can be mimicked by the DHT metabolite 3β-diol and by the subtype selective ERβ agonist DPN
  • E2 acts to enhance HPA reactivity
  • the ability of the ER antagonist tamoxifen, but not the AR antagonist flutamide, to block the inhibitory actions of DHT, speaks to the intracellular mechanism by which this inhibitory signal might be transduced.
    • Nathan Goodyear
      Nathan Goodyear on 15 Jul 15
       
      that is because the interaction with the DHT metabolite is not with the AR, but with the ER-beta.
  • the DHT metabolite 3β-diol and the ERβ-subtype-selective agonist DPN suppressed ACTH, corticosterone, and c-fos mRNA responses to restraint stress in a manner similar to DHT
  • metabolism of DHT to 3β-diol and subsequent binding to ERβ can be inhibitory to HPA reactivity, and this is one possible mechanism for the action of DHT.
  • Our data also suggest that E2 enhances the reactivity of the HPA axis to stress by acting on or near neurons of the PVN
  • the actions of E2 appear to be through an ERα-dependent mechanism
  • these studies suggest that ERβ, within the male hypothalamus, acts to inhibit the HPA axis and that the inhibitory effects of DHT may be, at least in part, via its intracellular conversion to 3β-diol and subsequent binding to ERβ
  • Nathan Goodyear on 15 Jul 15
     
    DHT metabolites: particularly 3beta-androstanediol inhibit HPA axis through ER-beta.
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

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

www.nature.com/srep01528

androgen metabolites prostate prostate cancer hormones DHT dihydrotestosterone

shared by Nathan Goodyear on 05 Oct 16 - No Cached
  • Nathan Goodyear on 05 Oct 16
     
    good review of androgen metabolites and prostate cancer.
Nathan Goodyear

Anticancer Testosterone Metabolite 3β-Adiol (July 2012) Townsend Letter for D... - 0 views

www.townsendletter.com/...anticancer0712.html

testosterone metabolite metabolites testosterone metabolites 3-beta androstanediol androgen androgens hormone hormones

shared by Nathan Goodyear on 14 May 13 - No Cached
  • Nathan Goodyear on 14 May 13
     
    interesting read on the testosterone metabolite 3beta androstanediol.
Nathan Goodyear

Urinary concentrations of di(2-ethylhexyl) phthalat... [J Androl. 2011] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...21597090

low T testosterone free androgen index urinary phthalate metabolites DEHP MEHP MEHHP MEOHP

shared by Nathan Goodyear on 12 Dec 11 - No Cached
  • three metabolites of DEHP [mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)] were inversely associated with the free androgen index (FAI = T/SHBG) and calculated free testosterone (FT)
  • Nathan Goodyear on 12 Dec 11
     
    analysis of 3 urinary phthalate metabolites found to be associated with low free androgen index and a low free Testosterone
Nathan Goodyear

Effect of dehydroepiandrosterone derivatives... [Bioorg Med Chem. 2014] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...25261928

5alpha reductase DHEA metabolites hormone hormones

shared by Nathan Goodyear on 06 Oct 14 - No Cached
  • Nathan Goodyear on 06 Oct 14
     
    Interesting abstract of study of DHEA metabolites.  In vivo study finds some DHEA metabolites inhibit 5-alpha-reductase activity.  The opening sentence implies that 5alpha-reductase and conversion of T to DHT promotes androgen dependent disease.  The inference here is cancer, however, what they fail to mention is that this activity is via the estrogen receptors.
Nathan Goodyear

5alpha-androstane-3alpha,17beta-diol supports... [J Cell Biochem. 2008] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...18320593

5-alpha androstanediol 3-alpha androstanediol DHT metabolite prostate cancer hormone hormones metabolites androgen receptors AR estrogen ER

shared by Nathan Goodyear on 23 Jan 14 - No Cached
  • Nathan Goodyear on 23 Jan 14
     
    5 alpha androstanediol promotes prostate cancer growth and survival independent of androgen receptors.   This study didn't clarify the mechanism.  We no know that this occurs via estrogen receptor alpha.  Thus a Testosterone metabolite signals through an estrogen receptor.
Nathan Goodyear

British Journal of Cancer - Androgen metabolism in prostate cancer: from molecular mech... - 0 views

www.nature.com/...bjc2014268a.html

androgens metabolites hormones hormone Testosterone DHT 3 alpha-androstanediol 3 beta androstanediol cancer

shared by Nathan Goodyear on 15 Jul 15 - No Cached
  • Nathan Goodyear on 15 Jul 15
     
    androgen metabolites and prostate cancer promotion.
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

shared by Nathan Goodyear on 27 Jan 14 - No Cached
  • 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

https://www.jstage.jst.go.jp/article/jmi/61/1.2/61_35/_pdf - 0 views

www.jstage.jst.go.jp/..._pdf

prostate cancer PSA Testosterone men male hormone hormones androgen deprivation therapy

shared by Nathan Goodyear on 09 Apr 14 - No Cached
  • Nathan Goodyear on 09 Apr 14
     
    study looked at androgen deprivation therapy in non-metastatic prostate cancer.  This study found that the elimination of ADR post 5 years was associated with low recurrence.  Relapse of increased PSA was associated with increasing Testosterone off of ADR.  This study did not look at estrogens or androgen metabolites.  Too short sided in its design.
Nathan Goodyear

The Androgen 5α-Dihydrotestosterone and Its Metabolite 5α-Androstan-3β, 17β-D... - 0 views

www.jneurosci.org/...1448.long

DHT metabolite metabolites 3-beta androstanediol 3-beta-diol HPA stress ER estrogen receptor ER beta ER-beta hormone hormones

shared by Nathan Goodyear on 03 Feb 14 - No Cached
  • Nathan Goodyear on 03 Feb 14
     
    Full article of previously posted abstract.  DHT metabolite 3beta-diol inhibits HPA stress response via ER beta.  
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

shared by Nathan Goodyear on 27 Jan 14 - No Cached
  • Nathan Goodyear on 27 Jan 14
     
    Good review of intra-tumor androgen synthesis from DHT metabolites.
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.
Nathan Goodyear

Dihydrotestosterone may inhibit hypothalamo-pi... [Neurosci Lett. 2004] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...15234470

hormone hormones DHT metabolite metabolites 3-beta androstanediol 3-beta-diol ER estrogen receptor ER beta ER-beta

shared by Nathan Goodyear on 03 Feb 14 - No Cached
  • Nathan Goodyear on 03 Feb 14
     
    Mouse study finds that DHT metabolite provides negative feedback to HPA via 3beta androstaendiol.  What is interesting is that this signaling occurred through ER beta.  Androgen signaling processed through estrogen receptors.
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