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Nathan Goodyear

Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities. - 0 views

genesdev.cshlp.org/...2266.full.pdf+html

progesterone inflammation PR receptors PR-A PR-B

shared by Nathan Goodyear on 09 Nov 12 - No Cached
  • Nathan Goodyear on 09 Nov 12
     
    study shows that mice lacking PR-A and PR-B (progesterone receptors) have increased uterine inflammation.   Again, the inflammatory/pro-inflammatory effects of hormones may be regulated through receptors.  This may be the reason that different stages of life elicit a different response with the same hormone.
Nathan Goodyear

NK Cells Expressing a Progesterone Receptor Are Susceptible to Progesterone-Induced Apo... - 0 views

www.jimmunol.org/...5746.full

progesterone PR receptors NK cell reproduction infertility immunity

shared by Nathan Goodyear on 14 May 12 - No Cached
  • Nathan Goodyear on 14 May 12
     
    NK cells have progesterone receptors.  This has important immunologic and reproductive impact.
Nathan Goodyear

A Novel Antiestrogenic Mechanism in Progesterone Receptor-transfected Breast Cancer Cells - 0 views

www.jbc.org/...17480.short

progesterone progesterone receptors hormones ER breast cancer

shared by Nathan Goodyear on 12 Oct 16 - No Cached
  • Nathan Goodyear on 12 Oct 16
     
    Progesterone receptor activation found to block proliferative estradiol effect in breast cancer cell lines.
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

Immunohistochemical Expression of Estrogen and Progesterone Receptors in Human Colorect... - 0 views

www.ncbi.nlm.nih.gov/...PMC3215447

estrogen progesterone ER estrogen receptor estrogen receptors ER alpha ER beta ER-alpha ER-beta PR progesterone receptor progesterone receptors

shared by Nathan Goodyear on 09 Jun 14 - No Cached
  • Nathan Goodyear on 09 Jun 14
     
    Study finds ER and PR increase along the timeline of tumor initiation.  The authors point to likely association that ER and PR expression is associated with and key to initiating colorectal transformation.  A lot to be determined from this study.  IF this were entirely true, then what to explain the 35% lower colorectal cancer risk in women vs men?  Likely ER and PR pertubance plays a significant role is likely, but the mere expression--yet to be determined.
Nathan Goodyear

Mapping and Characterization of the Functional Domains Responsible for the Differential... - 0 views

www.jbc.org/...32889.long

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

shared by Nathan Goodyear on 27 Nov 12 - No Cached
  • Nathan Goodyear on 27 Nov 12
     
    different functions of PR-A and PR-B.
Nathan Goodyear

Progesterone Receptor Inhibits Aromatase and Inflammatory Response Pathways in Breast C... - 0 views

mend.endojournals.org/...1812.long

progesterone receptor receptors PR breast cancer anti-inflammatory

shared by Nathan Goodyear on 12 Nov 12 - No Cached
  • Nathan Goodyear on 12 Nov 12
     
    Progesterone receptor (PR) shown to provide an important anti-inflammatory role in breast cancer in this study.  PR shown to increase NF-kappaB inhibitor IkBalpha, shown to inhibit aromatase activity, shown to inhibit COX-2 expression and shown to inhibit HER-2/neu expression.
Nathan Goodyear

Papillary Thyroid Carcinoma: Differential Diagnosis and Prognostic Values of Its Differ... - 0 views

www.hindawi.com/...915925

papillary thyroid cancer estrogen progesterone receptors

shared by Nathan Goodyear on 25 Nov 13 - No Cached
  • Nathan Goodyear on 25 Nov 13
     
    columnar cell variant of papillary cancer associated with increased estrogen and progesterone nuclear receptor expression.  However, when you read this study, the more aggressive tumors were associated with a decrease in progesterone expression.
Nathan Goodyear

Progesterone inhibits mature rat dendritic cells in a receptor-mediated fashion - 0 views

intimm.oxfordjournals.org/...287.long

progesterone inflammation dendritic cells T cell Th1 hormone hormones

shared by Nathan Goodyear on 09 Nov 12 - No Cached
  • Nathan Goodyear on 09 Nov 12
     
    study shows that progesterone directly inhibits pro-inflammatory cytokine signaling in rat dendritic cells.  Progesterone here shows to be directly involved in a anti-inflammatory effect.
Nathan Goodyear

Membrane 5α-pregnane-3,20-dione (5αP) receptors in MCF-7 and MCF-10A breast c... - 0 views

www.sciencedirect.com/...S0960076005003420

breast cancer progesterone metabolites progesterone metabolites hormone hormones

shared by Nathan Goodyear on 18 Jun 14 - No Cached
  • Nathan Goodyear on 18 Jun 14
     
    Very interesting study.  In ER/PR + breast cancer cells, Estradiol and 5alpha-dihydroprogestorone increase the membrane expression of 5alpha-dihydroprogesterone receptors.  This has a pro-growth, pro-metastatic potential.  In contrast, the metabolites 3alpha-dihdroprogesterone and 20alpha-HP inhibit the same membrane receptor expression thus giving an antigrowth, anti-metastatic potential.
Nathan Goodyear

5'-Heterogeneity in human progesterone recept... [Mol Endocrinol. 1990] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...2082185

progesterone receptors PR PR-A PR-B PR-C human

shared by Nathan Goodyear on 09 Nov 12 - No Cached
  • Nathan Goodyear on 09 Nov 12
     
    article describes 3 progesterone receptors: A, B, and C.
Nathan Goodyear

Leptin and Androgens in Male Obesity: Evidence for Leptin Contribution to Reduced Andro... - 0 views

press.endocrine.org/...jcem.84.10.6082

obesity leptin low T low Testosterone Testosterone low T leydig cells LH leutenizing hormone men male hormones hormone

shared by Nathan Goodyear on 04 Sep 14 - No Cached
  • in male obesity basal and LH-stimulated androgen levels are reduced and inversely correlated with circulating leptin
  • functional leptin receptors are present in rodent Leydig cells
  • it is conceivable that in males high leptin concentrations may have a direct inhibitory effect(s) on Leydig cell function.
  • ...18 more annotations...
  • insulin is an important inhibitor of the synthesis of SHBG
  • no correlation between leptin and SHBG levels
  • SHBG reduction in obesity is a minor determinant of lowered androgen levels
  • SHBG can explain only up to 3% of the correlation
  • testicular T de novo production is impaired in obese men and that leptin seems to be the best hormonal predictor of this blunted response to LH stimulation
  • The low basal 17-OH-P levels found in massively obese men are consistent with a global impairment of Leydig cell steroidogenic function in this group of subjects.
  • These findings indicate that obese men have a FM-related defect in the enzymatic conversion of 17-OH-P to T, which is revealed by hCG stimulation.
  • Other studies have investigated the adrenal function in male obesity and have shown that basal cortisol and 17-OH-progesterone levels tend to decrease with the increase in the degree of obesity
  • High E2 can inhibit the expression and activity of the 17,20-lyase and may be responsible for this steroidogenic lesion
  • However, stimulated E2 levels were not higher in the obese than in controls, excluding the fact that the lower androgen response was due to an increased aromatization of T to E2 and that estrogens have a major role in the observed defect of 17,20-lyase activity in obese men.
  • the percentage increase in the 17-OH-progesterone to T molar ratio paralleled the increase in leptin levels of obese men
  • Multiple regression analysis indicated that the best hormonal predictor of the obesity-related reduction in T and FT basal levels and androgen changes after hCG stimulation was serum leptin concentration
  • insulin has no negative influences on androgen production in obese men
  • insulin is known to have stimulatory actions on T production that have been demonstrated in obese and normal weight men (57) and in Leydig cells in culture
  • the negative correlation between insulin and basal T can be partly explained by the inhibitory action of insulin on SHBG production
  • hypogonadal men have higher circulating leptin levels compared with hypogonadal patients under effective androgen substitution therapy
  • The impaired androgen response to LH stimulus was due to a defect in the enzymatic conversion of 17-OH-progesterone to T, which was disclosed by a leptin-related increase in 17-OH-progesterone to T ratio
  • Estrogens, which are inhibitory modulators of LH pulsatility and bioactivity
  • Nathan Goodyear on 04 Sep 14
     
    Leptin appears to be a good marker of low Testosterone.  This study proposes that the mechanism of action is potentially 2 fold: first, a decrease in LH release by leptin (kisspeptin?) and 2nd, a directed decrease in Testosterone production by the leydig cells in the testes.
Nathan Goodyear

ScienceDirect.com - Fertility and Sterility - Intact progesterone receptors are essenti... - 0 views

www.sciencedirect.com/...S001502820400980X

progesterone PR ER-alpha ER-beta receptor receptors inflammation endometriosis Estradiol

shared by Nathan Goodyear on 12 Nov 12 - No Cached
  • Nathan Goodyear on 12 Nov 12
     
    mice model, but progesterone deficiency results in decreased PR expression to provide counter anti-inflammatory effect in endometriosis model.  Thus pro-inflammatory transcription via E2 through ER signaling.  It would be interesting to see if that was ER-alpha or ER-beta.
Nathan Goodyear

Use of Different Postmenopausal Hormone Therapies and Risk of Histology- and Hormone Re... - 0 views

ascopubs.org/...JCO.2007.13.4338

breast cancer cancer progesterone hormones

shared by Nathan Goodyear on 09 Dec 16 - No Cached
  • Nathan Goodyear on 09 Dec 16
     
    natural progesterone decreased the risk of breast cancer caused by long term use of estrogens in study of 80,000+.  I would have been nice to have seen a progesterone only arm of the study.
Nathan Goodyear

Is There an Association Between Meningioma and Hormone Replacement Therapy? - 0 views

jco.ascopubs.org/...279.full

meningioma hormones estrogen receptors estrogen receptor brain tumors progesterone receptors progesterone

shared by Nathan Goodyear on 05 Feb 13 - No Cached
  • Nathan Goodyear on 05 Feb 13
     
    Hormones linked to increase meningioma in women.   Clearly, the evidence shows that hormone receptors play a significant role in the growth and the potential management of these tumors.
Nathan Goodyear

http://www.turkjcancer.org/pdf/pdf_TJC_489.pdf - 0 views

www.turkjcancer.org/...pdf_TJC_489.pdf

colon colorectal cancer ER PR estrogen receptor estrogen receptors progesterone receptor progesterone receptors

shared by Nathan Goodyear on 09 Jun 14 - No Cached
  • Nathan Goodyear on 09 Jun 14
     
    The relationship between ER and PR and colorectal cancer is yet to be determined.  It is not outside the realm of possibility that a standardization of ER/PR in colorectal cancer is unlikely.  Each cancer is unique.  There are probably some generalizations that can be made, but complete generalizations of ER/PR in colorectal cancer in women is unlikely.
Nathan Goodyear

The dialectic role of progesterone. [Maturitas. 2009] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...19171445

progesterone metabolite metabolites. hormone hormones receptor PR-A PR-B

shared by Nathan Goodyear on 30 Jan 14 - No Cached
  • Nathan Goodyear on 30 Jan 14
     
    knowledge of progesterone and its metabolites are important in the use of hormones.  As the authors concluded here: "natural steroids should not be disparaged...an update on endocrinological knowledge and experience is rather mandatory for gynecologists".  There in lies the problem.  The IOM has shown that the average physician practices at a level of 17 years behind the current scientific knowledge and the environment created by medical governing bodies discourages questions, so as to protect the system.
Nathan Goodyear

Estrogen receptor-alpha expression in human meningiomas - 0 views

igitur-archive.library.uu.nl/...c8.pdf

meningioma hormone receptors hormone receptor hormones estrogen receptor ER alpha PR progesterone receptor

shared by Nathan Goodyear on 05 Feb 13 - No Cached
  • Nathan Goodyear on 05 Feb 13
     
    This is a dissertation, but they found ER alpha expression in all meningioma samplings. This is in contrast to previous studies. As further research has come with meningiomas, more ER presence is found, likely due to improved testing techniques. What is interesting here is that Low/no PR status was associated with Increased ER alpha status. This has been shown to be a more pro-inflammatory/pro-growth picture in disease states, such as breast and prostate CA.
Nathan Goodyear

The implication of neuroactive steroids in Tourette syndrome pathogenesis: a ... - 0 views

www.ncbi.nlm.nih.gov/...PMC3849218

tourette's syndrome hormones 5-alpha reductase

shared by Nathan Goodyear on 08 Dec 15 - No Cached
  • The typical onset of TS occurs at 6–7 years of age and is characterized by the appearance of simple, recurrent motor tics, followed by the manifestation of phonic tics after several months [12]. In most children, TS symptoms undergo a progressive exacerbation, which reaches its zenith at the beginning of puberty (11–12 years of age), and is then followed by a gradual remission in the majority of patients
  • 30–40% of TS-affected children retain their symptoms in adulthood
  • Multiple neurotransmitters have been implicated in TS, including dopamine (DA), serotonin, norepinephrine, acetylcholine, glutamate and γ-amino-butyric acid (GABA)
  • ...11 more annotations...
  • female gender may predict greater tic severity in adulthood
  • male gender is a major risk factor for TS (with a male:female prevalence ratio estimated at ~4:1)
  • the typical age of onset coincides with adrenarche (6–7 years old); symptoms increase in severity until the beginning of puberty (12 years old) and then undergo a spontaneous amelioration, which becomes apparent with the end of puberty (at 18–19 years of age)
  • TS is diagnosed later in females than males
  • ample evidence supports the involvement of DAergic dysfunctions in TS
  • a number of clinical observations showed that tics in TS patients could be exacerbated by anabolic androgens
  • steroidogenic enzymes and androgen receptors may serve as putative therapeutic targets for this disorder
  • Unlike males, tic severity is typically increased after puberty in females
  • 26% of females were found to experience exacerbation of tics in the estrogenic phase of the menstrual cycle, and this phenomenon was found to be correlated with increased tic severity at menarche
  • biochemical hallmark of adrenarche is the acquisition of 17,20 lyase activity by cytochrome P450 C17 (CYP17A1)
  • increased synthesis of dehydroepiandrosterone (DHEA) and androstenedione, which leads to the growth of axillary and pubic hair as well as enhancement in the oiliness of the skin
  • Nathan Goodyear on 08 Dec 15
     
    interesting read on hormones and tourette's.. Proposed that 5 alpha reductase activity is involved in worsening of tics.  This makes sense as Testosterone in men with low T is known to increase dopamine and dopaminergic dysfunction is known to play a role in tourette's;  the clinical presentation of girls vs boys is very different.  The authors of this article propose that 5 alpha reductase activity controls a back door method where by progesterone is converted to androgens.
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