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Nathan Goodyear

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

  • 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
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  • 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
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    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

Serenoa repens (Permixon) inhibits the 5alpha-r... [Int J Cancer. 2005] - PubMed - NCBI - 0 views

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    Saw Palmetto inhibits 5alpha reductase activity.  This study looked at the inhibition of Saw Palmetto of 5alpha reductase activity in prostate cancer.  Saw Palmetto is also known as Serenoa repens.
Nathan Goodyear

Expression of progesterone metabolizing enzyme genes (AKR1C1, AKR1C2, AKR1C3, SRD5A1, S... - 0 views

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    Breast cell culture study finds increase 5alpha-reductase 1/2 activity and decreased 3alpha HSO.  This fits previous previous studies that show that increased 5alpha pregnanes is associated with increased proliferation and increased detachment; in contrast to decreased 4-pregnene metabolites.
Nathan Goodyear

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

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    cell culture study finds that increased 5alpha reductase activity and resultant 5alpha-pregnanes are associated with breast cancer cell lines.  This is in contrast to the 4-pregnenes.  In fact, decreased 4-pregnenes are found in the same breast cancer cell lines; this suggests decreased 20alpha-HSO and 3alpha-HSO activity.
Nathan Goodyear

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

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    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

Progesterone metabolites in breast cancer - 0 views

  • In breast tumor tissue and tumorigenic cell lines, 5α-reductase activity and mRNA expression are significantly higher, whereas 3α- and 20α-HSO activities and mRNA expression are significantly lower than in normal breast tissue and nontumorigenic cells
  • Studies using various breast cell lines have shown that 5αP and 3αHP have opposing actions in terms of cell proliferation and adhesion; 5αP stimulates cell proliferation (through increased mitosis and decreased apoptosis) and cell detachment, whereas 3αHP suppresses cell proliferation (through decreased mitosis and increased apoptosis) and detachment
  • the paracrine/ autocrine functions of 5αP are cancer-promoting and those of 3αHP are cancer-inhibiting
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    Awesome article on progesterone metabolism in breast cancer.  The author, weibe, describes 2 categories of progesterone metabolites in breast tissue: 5alpha-pregnanes and 4-pregnenes.  The author describes 3 primary enzymes that control the balance between these 2 metabolites--5alpha reductase, 3alpha-HSO, and 20alpha-HSO.  The resultant balance of 5alpha-dihydroprogesterone and 3alpha-dihydroprogesterone helps to determine the cancer potential of breast tissue.
Nathan Goodyear

Androgen activation by 5α-reductase in patients with PCOS - 0 views

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    5alpha-reductase PCOS.  Insulin and obesity are associated with increased 5alpha-reductase activity.
Nathan Goodyear

Dutasteride affects progesterone metabolizing enzyme activity/expression in human breas... - 0 views

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    Cell culture study finds that 5alpha-reductase inhibition decreased 5alpha-pregnanes and thus inhibited cell proliferation and detachment; this is in contrast to the 4 pregnenes that occur through the enzymes 3alpha-hydroxysteroid oxidoreductase and the 20alpha-hydroxysteroid oxidoreductase, which show anti cell proliferation and cell detachment.
Nathan Goodyear

A preliminary investigation of the enzym... [J Herb Pharmacother. 2005] - PubMed - NCBI - 0 views

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    Saw Palmetto show to inhibit 5alpha reductase activity in prostate cancer cells.
Nathan Goodyear

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

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    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

BMC Cancer | Full text | Activity and expression of progesterone metabolizing... - 0 views

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    Might the enzymes be more important than the hormones themselves?  The number is important i.e. progesterone, but how the number came to be is more important as it points to the underlying etiology.  Here, the balance of enzymes are found to direct cell line tumor potential.  The enzyme 5alpha-reductase increased production of the 5alpha-pregnanes which increased tumor potential.  In contrast, the enzymes 20alpha-hydrosteroid oxidoreductase and 3alpha-hydroxysteroid oxidoreductase increase production of the 4alpha-pregnanes, which decreased tumor potential.
Nathan Goodyear

The Dark Side of 5α-Reductase Inhibitors' Ther... [Korean J Urol. 2014] - Pub... - 0 views

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    Nice review of the inherent risks associated with 5alpha-reductase inhibition therapy.
Nathan Goodyear

Use of 5α-reductase inhibitors for lower urinary tract symptoms and risk of p... - 0 views

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    5alpha reductase inhibitors associated with decreased risk of Gleason 2-7 prostate cancer in men with LUTS and enlarged prostate.
Nathan Goodyear

Potency of a novel saw palmetto ethanol extract, SP... [Adv Ther. 2010] - PubMed - NCBI - 0 views

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    Saw Palmetto extract found to be potent inhibitor of 5alpha reductase activity.   Inhibition was 61%.  This study looked at the inhibition in those men with BPH.
Nathan Goodyear

A randomized, double-blind, placebo-... [J Altern Complement Med. 2002] - PubMed - NCBI - 0 views

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    Study finds Saw Palmetto inhibits 5alpha reductase activity enough to show improvement in those with alopecia (hair loss).
Nathan Goodyear

A new approach to prostate cancer. [J Pharm Pharmacol. 1989] - PubMed - NCBI - 0 views

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    Progesterone is proposed as a therapy in prostate cancer.   The mechanism is due to the inhibition of 5alpha reductase activity.
Nathan Goodyear

Inhibition of Testosterone Conversion to Dihydrotestosterone in Men Treated Percutaneou... - 0 views

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    Progesterone to inhibit 5alpha reductase in men.
Nathan Goodyear

Progesterone-induced stimulation of mammary tumorigenesis is due to the proge... - 0 views

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    5 alpha reductase inhibitor, finasteride inhibits pro-tumor progesterone metabolite pathway.
Nathan Goodyear

Pre-receptor regulation of the androgen receptor - 0 views

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    Great read on the regulation of the androgen receptor by the different iso forms of 5-alpha reductase and HSD.
Nathan Goodyear

Androgens and prostate disease Cooper LA, Page ST - Asian J Androl - 0 views

  • intraprostatic androgens are not concomitantly increased when serum androgen levels are raised.
  • The "saturation model" proposes that the prostate is sensitive to very low concentrations of circulating androgens, but that once maximal AR binding is achieved, which occurs at relatively low concentrations of circulating T, further increases in serum T have little impact
  • men with metastatic prostate cancer given T who had been previously treated with castration had worsening of disease, whereas those without prior castration did not
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  • There is little data to support the withholding of T therapy on the basis of concern for precipitating prostate cancer.
  • Both intervention data and physiology studies point to minimal effects on the prostate gland when serum T levels are increased to the mid-normal range with T therapy
  • an individualized care plan to assess the possible risks and benefits of T therapy for each patient is critical to optimizing the use of androgens in male health.
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    Nice review of the mixed data on Testosterone and Prostate disease. It is clear that Testosterone does not precipitate prostate cancer.  The intraprostatic hormone milieu likely is different than that present in the serum.  No surprise there.  5alpha reductase decreases prostate volume, PSA, and low-grade prostate cancer, but actually increases aggressive prostate cancer. Supraphysiologic doping in young men associated with no increase in prostate disease. PSA no longer to be followed in men < 55.  Mortality rate not changed.  PSA change of 1.4 ng/ml is appropriate for additional prostate evaluation.  Testosterone therapy on average increased 0.5 ng/ml. Still, no mention of aromatase activity in this article.  Why is it that hormone sensitive disease in men is only with regards to androgens and women estrogen.
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