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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

ScienceDirect.com - The Journal of Steroid Biochemistry and Molecular Biology - Progest... - 0 views

www.sciencedirect.com/...S0960076009001216

progesterone progestins breast cancer receptors PR

shared by Nathan Goodyear on 15 May 12 - No Cached
  • Nathan Goodyear on 15 May 12
     
    this study states that progesterone promotes breast growth and has implications of breast cancer.  However, this study looked at progestins not progesterone.  Studies have shown a reduction of breast cancer risk with progesterone and an increase with progestins.  It would have been nice to have looked at "progesterone" metabolites.  This study shows the flaw that many have: the intermix progesterone and progestins as if they are one in the same and they are clearly not
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

shared by Nathan Goodyear on 17 Feb 12 - No Cached
  • 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

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

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

prostate cancer progesterone progesterone receptor hormones cancer prostate

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

Genomic agonism and phenotypic antagonism between estrogen and progesterone receptors i... - 0 views

advances.sciencemag.org/...e1501924.full

progesterone PR progesterone receptors progesterone receptor cancer breast cancer hormones

shared by Nathan Goodyear on 29 Jun 16 - No Cached
  • The presence and activity of PR significantly affect the prognostic value of ER.
  • The observed loss of PR protein expression in a subset of ER+/PR+ breast cancers, because of hypermethylation or deletion of the PR gene locus, results in the loss of ER prognostic value
  • These findings emphasize the clinical value of assessing both PR and ER expression in breast cancer samples
  • ...7 more annotations...
  • PR is an essential modulator of ER-regulated genes but also that it significantly contributes to the prognostic value of ER in ER+/PR+ breast cancers
  • PR-regulated genes have independent prognostic value, and the presence of PR correlates with favorable clinicopathological outcomes
  • this study demonstrates that progestin-activated PR redirects ER chromatin binding and functions as a genomic estrogen agonist and as a phenotypic estrogen antagonist in ER+/PR+ breast cancer cells and human tumors
  • Approximately 80% of ER+ breast cancers are also positive for PR,
  • In isolation, both hormones activate or inhibit cellular processes in similar directions, although the magnitude of these effects is less for progestin alone than for estrogen alone
  • PR-mediated antagonism of estrogenic phenotypes is well documented
  • joint activation of ER and PR antagonized ER-regulated oncogenic processes
  • Nathan Goodyear on 29 Jun 16
     
    WOW!!  study finds that progesterone through PR activity antagonizes ER protein expression by the cell.  This has huge implications in breast cancer and possible prostate cancer.  But then again, women don't need progesterone; only estrogen.  The presence of PR correlates with improved clinicopathological outcomes.  The authors do seem to get confused about progesterone and progestins.  They are not one in the same.
Nathan Goodyear

Progesterone Receptor-A and -B Have Opposite Effects on Proinflammatory Gene Expression... - 0 views

jcem.endojournals.org/...E719.abstract

progesterone progesterone receptors PR A PR B pregnancy anti-inflammatory labor

shared by Nathan Goodyear on 25 May 12 - No Cached
  • Nathan Goodyear on 25 May 12
     
    Progesterone is known to have anti-inflammatory action.  This study looked at the anti-inflammatory action of progesterone on the myometrium of the uterus during pregnancy.  The anti-inflammatory effect, in this study, was through Progesterone Receptor B.  There was a change in the dominance to PR A late in pregnancy.  This would promote inflammatory signaling and thus contractions with the onset of labor.
Nathan Goodyear

Harriet Lane Handbook: Progesterone regulates the phosphorylation of protein phosphatas... - 0 views

www.unboundmedicine.com/...ein_phosphatases_in_the_brain_

progesterone brain hippocampus cerebellum sex hormones hormone

shared by Nathan Goodyear on 11 Mar 14 - No Cached
  • Nathan Goodyear on 11 Mar 14
     
    rat model finds that progesterone effects internal cell enzyme activity.  In this case, progesterone increased PP2A in the cerebellum and in the hyippocampus.  Interesting, that E2 priming decreased the effects on the hippocampus, but not the cerebellum.  This reveals a biochemical link between sex hormones, progesterone in this case, and the brain.  Studies have shown progesterone to be neuroprotective in TBI.  This may be one mechanism.
Nathan Goodyear

Serum progesterone and prognosis in operable breast cancer. - 0 views

www.ncbi.nlm.nih.gov/...PMC2074551

progesterone breast cancer breast cancer survival

shared by Nathan Goodyear on 14 Oct 13 - No Cached
  • Nathan Goodyear on 14 Oct 13
     
    progesterone levels at the time of surgery predict outcome.  Higher progesterone levels associated with increased longevity.  progesterone > 4 ng/ml associated with 65% survival at 18 years versus 35% with those women and low progesterone.
Nathan Goodyear

Progesterone and estradiol in the saliva and plasm... [Am J Obstet Gynecol. 1983] - Pub... - 0 views

www.ncbi.nlm.nih.gov/...6638098

hormones hormone estradiol progesterone bioidentical saliva testing salivary

shared by Nathan Goodyear on 22 Nov 10 - No Cached
  • Nathan Goodyear on 22 Nov 10
     
    unbound progesterone and saliva progesterone are comparable; supports that salivary progesterone represents unbound progesterone in blood
Nathan Goodyear

Molecular Control of Immune/Inflammatory Responses: Interactions Between Nucl... - 0 views

edrv.endojournals.org/...435.long

progesterone NK macrophage T cell activity inflammation immune system

shared by Nathan Goodyear on 09 Nov 12 - No Cached
  • Nathan Goodyear on 09 Nov 12
     
    Benefits of progesterone, are in part, due to its function on the immune system.  Progesterone shown to decrease T cell activity, macrophage activity and NK cell activity.  Aside, NK cell activity has been found to be increased in those with recurrent first trimester miscarriages and progesterone defects.  So, low progesterone allows for a rise in NK cell activity and inflammation that is detrimental to a developing pregnancy.  If that is the case in pregnancy, what about the rest of the body?
Nathan Goodyear

Natural Killer Cells in Pregnancy and Recurrent Pregnancy Loss: Endocrine and Immunolog... - 0 views

edrv.endojournals.org/...44.full

natural killer cells pregnancy loss recurrent immune system miscarriage NK

shared by Nathan Goodyear on 15 Apr 12 - No Cached
  • NK cells have been the cells most extensively studied, primarily because they constitute the predominant leukocyte population present in the endometrium at the time of implantation and in early pregnancy
  • parental chromosomal abnormalities, uterine anatomic anomalies, endometrial infections, endocrine etiologies (luteal phase defect, thyroid dysfunction, uncontrolled diabetes mellitus), antiphospholipid syndrome, inherited thrombophilias, and alloimmune causes
  • estrogen
  • ...28 more annotations...
  • progesterone
  • prolactin
  • In summary, in vivo animal experiments have shown an inhibitory role of estrogen on peripheral NK cell lytic activity, which is partly due to suppression of NK cell output by the bone marrow and partly due to suppression of individual NK cell cytotoxicity. However, in vitro studies so far have failed to show conclusively a direct effect of estrogen on NK cells.
  • At the progesterone concentrations believed to be present in the uterus [up to 10−5 m at the maternal-fetal interface (35)], studies consistently show inhibition of lymphocyte proliferation (33) and inhibition of NK cytolytic activity in vitro
  • The exact role of prolactin in NK cell regulation is unknown.
  • The overall effects of estrogen on NK cells are likely multifactorial, therefore, and depend on the type of cell affected as well as the kind of ER expressed by that cell.
  • It is known that progesterone can directly affect T cell differentiation in vitro, suppressing development of the Th1 pathway and enhancing differentiation along the Th2 pathway (44)
  • Th1 cells predominantly produce interferon-γ (IFN-γ), IL-2, and TNF-β and are involved in cell-mediated immunity. Th2 cells produce IL-4, IL-5, IL-6, IL-10, and IL-13 and stimulate humoral immunity
  • Furthermore, in response to progesterone, γδ T cells produce progesterone-induced blocking factor (PIBF) (54
  • A defining characteristic of NK cells is their ability to lyse target cells without prior sensitization and without restriction by HLA antigens.
  • NK cell function is mainly regulated by IL-2 and IFN-γ
  • IL-2 causes both NK cell proliferation and enhanced cytotoxicity. IFN-γ augments NK cytolytic activity, but does not cause NK proliferation. The two cytokines act synergistically to augment NK cytotoxicity (6).
  • The largest leukocyte population in the endometrium consists of NK cells named large granulated lymphocytes
  • there is a significant increase in the number of uNK cells throughout the secretory phase, which peaks in early pregnancy when uNK cells comprise about 75% of uterine leukocytes (62)
  • Second, uNK cell phenotype changes during the normal menstrual cycle and early pregnancy (68)
  • general proinflammatory effect of estrogen, causing an influx of macrophages and neutrophils, which is antagonized by progesterone through its receptor (70, 71).
  • The mechanism of such a progesterone-induced local immunosuppression is unclear.
  • progesterone plays an important role in proliferation and differentiation of uNK cells (32).
  • Through promotion of a uterine Th2 environment, progesterone could indirectly affect uNK cell function
  • The mechanism of this increase in uNK cell numbers has been addressed in both human and mouse models, and is likely the result of: 1) recruitment of peripheral NK cells to the uterus, and 2) proliferation of existing uNK cells
  • prolactin system plays an important role in implantation and the maintenance of pregnancy
  • the exact pathways of hormonal regulation of NK cells remain to be delineated.
  • The exact function of uNK cells has not yet been unequivocally determined
  • uNK cells express a different cytokine profile, compared with resting peripheral NK cells. mRNAs for granulocyte CSF, M-CSF, GM-CSF, TNF-α, IFN-γ, TGF-β, and leukemia inhibitory factor (LIF) have been found in decidual CD56+ cells
  • Their increased numbers in early pregnancy, their hormonal dependence, and their close proximity to the infiltrating trophoblast all suggest that they play an important role in the regulation of the maternal immune response to the fetal allograft and the control of trophoblast growth and invasion during human pregnancy
  • role of uNK cell-derived cytokines on trophoblast growth and differentiation (114, 115, 116, 117).
  • Th1 immunity to trophoblast is associated with RPL, whereas Th2 immunity is associated with a successful pregnancy
  • RPL is associated with Th1 immunity, for which NK cells are partly responsible.
  • Nathan Goodyear on 15 Apr 12
     
    dysregulated immune system plays role in recurrent miscarriage.  Specifically, this article discusses natural killer cells (NK).
Nathan Goodyear

Regenerative potential for allopregnanolone - 0 views

pharmweb.usc.edu/...WangJ_BrainResRev57_2008.pdf

progesterone allopregnanolone hormone hormones BDNF neurodegeneration excitotoxicity Alzheimer's disease

shared by Nathan Goodyear on 10 Jul 12 - No Cached
  • Nathan Goodyear on 10 Jul 12
     
    Progesterone and allopregnanolone shown to have neuroprotective and neurogenesis properties in the brain. BDNF was positively correlated with progesterone. So as women age, progesterone falls, as progesterone falls, then BDNF falls and neuroplasticity declines and thus we see neurodegenerative disorders. And hormones are not needed? Who are these scientists that don't read research?!
Nathan Goodyear

Transdermal delivery of bioidentical proge... [J Pharm Pharm Sci. 2010] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...21486536

saliva salivary progesterone 5alpha reductase transdermal progesterone hormone hormones

shared by Nathan Goodyear on 08 Jul 13 - No Cached
  • Nathan Goodyear on 08 Jul 13
     
    Transdermal progesterone levels are quickly transported to saliva.  This quick transport, while serum doesn't equally reflect progesterone, has puzzled many.  Theories have been proposed, yet no answers.   This study looked at whether 5alpha reductase expression in the skin would metabolize the progesterone  and this explain the difference in the two test mediums.  The authors of this study concluded that 5alpha reductase is the not the reason for the difference found in saliva and serum.  the same can be applied to urine as well.
Nathan Goodyear

Differential regulation of endothelium behavior by progesterone and medroxyprogesterone... - 0 views

joe.endocrinology-journals.org/...179.abstract

progesterone medroxyprogesterone acetate medroxyprogesterone hormone hormones women cardiovascular disease HRT

shared by Nathan Goodyear on 04 Feb 14 - No Cached
  • Nathan Goodyear on 04 Feb 14
     
    No surprise that progesterone and the synthetic progestin medroxyprogesterone acetate (MPA) have different effects on the vascular endothelium. MPA inhibits NO production, whereas Progesterone maintains NO production.  MPA promoted platelet adhesion whereas Progesterone did not--significant implication in plaque formation.
Nathan Goodyear

Activity and expression of progesterone metabolizing 5α-reductase, 20α-hydrox... - 0 views

www.ncbi.nlm.nih.gov/...PMC154104

progesterone metabolites breast cancer 5alpha-reductase 5-alpha pregnene 5-alpha pregnenes 4-pregnene 4-pregnenes

shared by Nathan Goodyear on 30 Jan 14 - No Cached
  • Exposure of human breast cell lines (MCF-7, MCF-10A, and ZR-75-1) to 5α-pregnanes results in changes associated with neoplasia, including increased proliferation and decreased attachment [1], depolymerization of F-actin [2] and decreases in adhesion plaque-associated vinculin
  • Exposure to 4-pregnenes results, in general, in opposite (anti-cancer-like) effects
  • 5αR1 has been detected in various androgen-independent organs, such as the liver and brain
  • ...10 more annotations...
  • 5αR2 has been found predominantly in androgen-dependent organs, such as epididymis and prostate
  • The 5α-pregnanes:4-pregnenes ratio was about 8-fold higher in tumorous than in nontumorous breast tissue after an 8-hour incubation with [14C]progesterone
  • Studies with breast cell lines, showing that 5α-pregnanes stimulate proliferation and decrease attachment of cells
  • both tissue and breast cell line studies suggest that an elevated level of progesterone 5α-reductase activity may be an indicator of breast tumorigenesis, regardless of presence or absence of ER and/or PR
  • 5αR1 is the main isoform expressed in human breast carcinomas [29] and that 5αR2 may not be associated with risk of breast cancer
  • the differences in 5α-pregnane production between the cells is due primarily to a difference in 5αR1 expression
  • As in the case of 5α-reductase activity, the presence or absence of ER and PR do not appear to be related to 5α-reductase expression.
  • the conversion of progesterone to the cancer promoting 5α-pregnanes is significantly higher in the human tumorigenic breast cell lines
  • lthough both 5αR1 and 5αR2 are expressed by these cells, the elevated 5α-reductase activity appears to be the result of significantly greater expression of 5αR1
  • Changes in progesterone metabolizing enzyme expression (resulting in enzyme activity changes) may be responsible for promoting breast cancer progression due to increased production of tumor-promoting 5α-pregnanes and decreased production of anti-cancer 20α – and 3α-4-pregnenes
  • Nathan Goodyear on 30 Jan 14
     
    balance of enzyme production between 5alpha-reductase and 20alpha-hydroxysteroid oxidoreductase and 3alpha(beta)-hydroxysteroid oxidoreductase play role in carcinogenesis and proliferation in the balance of production of progesterone metabolites. The 5alpha pregnenes are pro carcinogenic  and the 4-pregnenes are anti carcinogenic.
Nathan Goodyear

Progesterone neuroprotection in trauma... [Front Neuroendocrinol. 2009] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...19318112

progesterone myelin BDNF traumatic brain injury TBI head trauma

shared by Nathan Goodyear on 19 Mar 14 - No Cached
  • Nathan Goodyear on 19 Mar 14
     
    Progesterone has a neuroprotective and promyelinating effects in the nervous system.  Progesterone increases BDNF.  Progesterone increases proliferation and differentiation of oligodendrocyte progenitor cells which will increase myelin production.
Nathan Goodyear

The Role of Progesterone in Traumatic Brain Injury : The Journal of Head Trauma Rehabil... - 0 views

journals.lww.com/..._Traumatic_Brain_Injury.6.aspx

progesterone TBI brain injury traumatic brain injury head trauma hormone hormones

shared by Nathan Goodyear on 17 Mar 14 - No Cached
  • Nathan Goodyear on 17 Mar 14
     
    Progesterone useful in inflammation reduction in Traumatic Brain Injuries.  This applies to both sexes.
Nathan Goodyear

Revisiting the roles of progesterone and allo... [Prog Neurobiol. 2014] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...24172649

progesterone metabolites metabolite allopregnanolone GABA receptors PR brain

shared by Nathan Goodyear on 17 Mar 14 - No Cached
  • Nathan Goodyear on 17 Mar 14
     
    Only the abstract is available, but this study looks at the effects of progesterone through progesterone receptors and the progesterone metabolite allopregnanolone via the GABA A receptors in the brain.
Nathan Goodyear

Caution on the use of saliva measurements to monitor absorption of progesterone from tr... - 0 views

www.maturitas.org/...abstract

saliva measurements salivary testing hormone progesterone

shared by Nathan Goodyear on 12 Jul 11 - No Cached
  • Nathan Goodyear on 12 Jul 11
     
    conclusion incorrect.  blood testing is a poor testing method of transdermal progesterone therapy would be the more accurate conclusion.  Other studies have shown that transdermal progesterone therapy raises progesterone in saliva when blood levels show no change.
Nathan Goodyear

Breast Cancer Research | Full text | Progesterone receptors - animal models and cell si... - 0 views

breast-cancer-research.com/...182

PR-A PR-B PR progesterone receptor progesterone receptors progesterone receptor

shared by Nathan Goodyear on 27 Nov 12 - No Cached
  • Nathan Goodyear on 27 Nov 12
     
    good discussion on progesterone receptors, coactivators, corepressors and their impact on breast cancer.  The question is, do these findings have applications to non-disease.
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