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Nathan Goodyear

Testosterone and Estradiol Regulate Free Insulin-Like Growth Factor I (IGF-I), IGF Bind... - 0 views

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    testosterone and Estradiol effect IGF-1 levels.  This small study looked at 8 men and 8 postmenopausal women.  Findings:  low testosterone and high estradiol decrease IGF-1 availability.   Estradiol in postmenopausal women will result in a decrease in IGF-1 through an elevation of IGFBP-1.  In men, testosterone replacement stimulates increased HGH secretion and resultant IGF-1 secretion
Nathan Goodyear

Which Patients Do Not Require a GH Stimulation Test for the Diagnosis of Adult GH Defic... - 0 views

  • Four studies have reported that the probability of GHD (peak GH criteria ranging from < 2.3 to < 5 μg/liter) in patients with three to four PHDs ranges from 91% to 100%
  • 95% accuracy by the presence of either three or more PHDs or a serum IGF-I concentration less than 84 μg/lite
  • adult GHD could be predicted with 95% accuracy by the presence of either three or four PHDs or a serum IGF-I concentration less than 84 μg/liter
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  • Hypopituitary adults with GHD have been reported to have normal serum IGF-I levels in 37–70% of patients in various studies (5, 9, 18, 21, 22). This is owing in part to the fact that multiple factors regulate serum IGF-I concentrations including nutritional status; hepatic and renal function; and circulating concentrations of thyroid hormone, androgens, and estrogens
  • changes in concentrations of IGF-binding proteins (IGFBPs) influence the total concentration of IGF-I in plasma
  • Among patients with an IGF-I sd score above −1 in the present study, 46% had a peak GH less than 2.5 μg/liter and 67% had a peak GH less than 5 μg/liter.
  • In summary, adult GHD can be predicted with 95% accuracy by the presence of either three or four PHDs or a serum IGF-I concentration less than 84 μg/liter
  • We propose that adult patients with three or four PHDs (three or four of the following deficiencies: TSH, ACTH, gonadotropins [LH and/or FSH], and AVP [central diabetes insipidus]) do not require a GH stimulation test to make the diagnosis of adult GHD
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    Insulin Tolerance Test is the gold standard for HGH diagnosis, but this an unpopular test do to long list of side effects.  This study finds a 95% accuracy for IGF-1 less than 84 with 3 or more coexisting pituitary hormone deficiencies.
Nathan Goodyear

A cross-sectional study of different patterns of oral contraceptive use among premenopa... - 0 views

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    Birth control pills were found to reduce IGF-1 levels in the short term and long term.  Those that had used birth control pills had lower IGF-1 levels compared to those that had never used birth control pills.  This fits with the current knowledge that oral estrogen reduces HGH and IGF-1.  Those were in post-menopausal women, but this is in pre-menopaus women.  This has implications on health, weight, disease...
Nathan Goodyear

http://annonc.oxfordjournals.org/content/12/11/1533.full.pdf#page=1&view=FitH - 0 views

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    Study finds link between higher glycemic index and glycemic load with increased breast cancer risk.   The proposed mechanisms are: hyperinsulinemia and its affinity for IGF-1 receptor resulting in a + growth signal.  Increased IGF-1 via the same mechanism. Insulin and IGF-1 have negative regulation effects on SHBG. This all makes sense as insulin receptors are highly expressed on cancer cells.
Nathan Goodyear

Sensitivity and specificity of six tests for the diagnosis of adult... - PubMed - NCBI - 0 views

  • ARG plus GHRH test, high sensitivity (96 and 95%, respectively) and specificity (92 and 91%, respectively) for GH deficiency were achieved
  • The greatest diagnostic accuracy occurred with the ITT and the ARG plus GHRH test
  • 95% specificity could be achieved with the ARG plus L-DOPA and ARG tests only with very low peak GH cut-points (0.25 and 0.21 microg/liter, respectively) and not at all with the L-DOPA test
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  • Although serum IGF-I levels provided less diagnostic discrimination than all five GH stimulation tests, a value below 77.2 microg/liter was 95% specific for GH deficiency
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    study evaluated 6 tests for HGH deficiency diagnosis.  Ninety-five percent specificity found with ARG + l-DOPA and ARG alone.  However, the authors found a 95% specificity with IGF-1 < 77.  Although, IGF-1 is false negative in up to 65% of those with HGH deficiency.
Nathan Goodyear

Diagnosing Growth Hormone Deficiency in Adults - 0 views

  • it is clear that serum IGF-1 and or IGFBP-3 can be normal in patients with undisputed GHD
  • Various investigators have reported normal IGF-1 values in 37–70% of GH deficient adults
  • The co-administration of arginine and GHRH (the combined test) is a powerful stimulus for GH production and has gained increasing acceptance as a useful method of diagnosing GHD [34]. This test has been advocated as a suitable alternative to ITT
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  • The glucagon stimulation test (GST) is a reliable, safe alternative to the ITT in the diagnosis of GHD
  • An intravenous infusion of arginine (0.5 g/kg body weight) together with an intravenous bolus of GHRH (1 mcg/kg body weight) is administered [30]. Serum samples for GH are then obtained every 15–30 minutes for two hours.
  • Obesity, particularly marked obesity, is associated with blunted GH secretion in response to provocative stimuli
  • It has also been suggested that that even mildly increased BMI (25–30 kg/m2) can result in diminished stimulated GH production in 13% of healthy subjects
  • Corneli et al. have defined BMI-specific cut-off points for diagnosing adult-onset GHD using GHRH + arginine—11.5 ng/mL for those with BMI &lt; 25 kg/m2, 8.0 ng/mL for BMI 25–30 kg/m2, 4.2 ng/mL for those with BMI &gt; 30 kg/m2
  • GH levels are higher during the luteal phase in comparison with the follicular phase of the cycle
  • Oral, in contrast to transdermal oestrogen, lowers IGF-1 levels and is associated with increased GH levels
  • Adequate pituitary replacement with thyroxine and hydrocortisone are needed for optimal GH production
  • one cannot rely on a low IGF-1 to diagnose GHD in women taking oral oestrogen preparations.
  • Numerous GH secretagogues are available with the insulin tolerance test being the gold standard and the glucagon stimulation test or the GHRH + arginine as acceptable alternatives
  • ain et al. found the GST to be at least as good as the ITT in provoking GH secretion
  • the GST is safe, with almost no contraindications, it causes nausea and sometimes vomiting in 15–20% of subjects
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    Nice, more recent analysis, of HGH testing.
Nathan Goodyear

Testosterone administration to elderly men increases skeletal muscle strength and prote... - 0 views

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    Testosterone given to elderly men with low "serum" testosterone shown to increase IGF-1 and increased muscle growth and strength.  So, this study shows that testosterone in men, seems to increase HGH production and thus increase IGF-1 production.  This may be the mechanism by which testosterone promotes muscle growth and increase in strength in men.
Nathan Goodyear

Insulin-like growth factor receptor-1 (IGF-IR) as a target for prostate cancer therapy - 0 views

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    Insulin and IGF-1 receptors show 70% homology.
Nathan Goodyear

Communication between genomic and non-genomic signaling events coordinate steroid hormo... - 0 views

  • steroid hormones typically interact with their cognate receptor in the cytoplasm for AR, glucocorticoid receptor (GR) and PR, but may also bind receptor in the nucleus as appears to often be the case for ERα and ERβ
  • This ligand binding results in a conformational change in the cytoplasmic NRs that leads to the dissociation of HSPs, translocation of the ligand-bound receptor to the nucleus
  • In the nucleus, the ligand-bound receptor dimerizes and then binds to DNA at specific HREs to regulate gene transcription
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  • some steroid hormone-induced nuclear events can occur in minutes
  • the genomic effects of steroid hormones take longer, with changes in gene expression occurring on the timescale of hours
  • Classical steroid hormone signaling occurs when hormone binds nuclear receptors (NR) in the cytoplasm, setting off a chain of genomic events that results in, among other changes, dimerization and translocation to the nucleus where the ligand-bound receptor forms a complex with coregulators to modulate gene transcription through direct interactions with a hormone response element (HRE)
  • NRs have been found at the plasma membrane of cells, where they can propagate signal transduction often through kinase pathways
  • Membrane-localized ER, PR and AR have been reported to modulate the activity of MAPK/ERK, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), nitric oxide (NO), PKC, calcium flux and increase inositol triphosphate (IP3) levels to promote cell processes including autophagy, proliferation, apoptosis, survival, differentiation, and vasodilation
  • ERα36, a 36kDa truncated form of ERα that lacks the transcriptional activation domains of the full-length protein. Membrane-localized ERα36 can activate pathways including protein kinase C (PKC) and/or mitogen activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) to promote the progression of various cancers
  • G protein-coupled receptor 30 (GPR30), also referred to as G protein-coupled estrogen receptor (GPER), is a membrane-localized receptor that has been observed to respond to estrogen to activate rapid signaling
  • hormone-responsive G protein coupled receptor is Zip9, which androgens can activate
  • GPRC6A is another G protein-coupled membrane receptor that is responsive to androgen
  • androgen-mediated non-genomic signaling through this GPCR can modulate male fertility, hormone secretion and prostate cancer progression
  • non-NR proteins located at the cell surface can bind to steroid hormones and respond by eliciting rapid signaling events
  • Estrogens have been shown to induce rapid (i.e. seconds) calcium flux via membrane-localized ER (mER)
  • ER-calcium dynamics lead to activation of kinase pathways such as MAPK/ERK which can result in cellular effects like migration and proliferation
  • 17β-estradiol (E2) has been reported to promote angiogenesis through the activation of GPER
  • Membrane NRs may also mediate rapid signaling through crosstalk with growth factor receptors (GFR)
  • A similar crosstalk occurs between the receptor tyrosine kinase insulin-related growth factor-1 receptor (IGF-IR) and ERα. Not only does IGF-IR activate ERα, but inhibition of IGF-IR downregulates estrogen-mediated ERα activity, suggesting that IGF-IR is essential for maximal ERα signaling
    • Nathan Goodyear
       
      This is a bombshell that shatters the current right brain approach to ER. It completely shatters the concept of eat sugar, whatever you want, with cancer treatment in ER+ or hormonally responsive cancer!
  • Further, ER activates IGF-IR pathways including MAPK
  • GPER is involved in the transactivation of the EGFR independent of classical ER
  • tight interconnection between genomic and non-genomic effects of NRs.
  • non-genomic pathways can also lead to genomic effects
  • androgen-bound AR associates with the kinase Src at the plasma membrane, activating Src which then leads to a signaling cascade through MAPK/ERK
  • However, Src can also increase the expression of AR target genes by the ligand-independent transactivation of AR
  • extranuclear steroid hormone actions can potentially reprogram nuclear NR events
  • estrogen modulated the expression of several genes including endothelial nitric oxide synthase (eNOS) via rapid signaling pathways
  • epigenetic changes can then mediate genomic events in uterine tissue and breast cancer cells
Nathan Goodyear

Nutrition & Metabolism | Full text | Over-stimulation of insulin/IGF-1 signaling by Wes... - 0 views

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    Elevated insulin and IGF-1 as a result of the typical western diet results in increased risk of many of the chronic diseases of aging that we see in America--cancer.
Nathan Goodyear

Aging, Atherosclerosis, and IGF-1 - 0 views

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    good article discussing the positive impact of IGF-1 on atherosclerosis.  This hormone, under the control of HGH, is important in the healing and regenerative process.  Thus, the use of the term "anti-aging".  However, these two hormones simply help the body heal, repair, and regenerate itself.  Not surprising, inflammation (TNF-alpha) counteracts these positive effects.
Nathan Goodyear

Analysis of Relations between serum levels of Epitestosterone, Estradiol, Testosterone,... - 0 views

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    Great confusion exists in the medical profession about Testosterone and PSA and the health of the prostate. The conversion of Estrogen, whether E2 or E1, and other variables are responsible for increases in PSA while on Testosterone therapy. This study points out that Estradiol in men stimulates cell line growth of prostate cancer. In contrast, Epitestosterone, an androgen metabolite, has antiandrogen, inhibits this estrogen activity. Epitestosterone exists in an inverse relationship to Estradiol and IGF-1.
Nathan Goodyear

Protein Restriction, Epigenetic Diet, Intermittent Fasting as New Approaches for Preven... - 0 views

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    Calorie restriction and protein restriction inhibit IGF-1, insulin, AkT, PI3K, and mTOR. In addition, those with protein intake >20%, compared to 10%, was associated with a 4 fold increase in cancer death risk and a 75% increase in overall mortality. Protein restriction inhibits tumor growth, associated with a 30-70% reduction in IGF-1, reduced the accumulation of oxidized proteins. The restriction of tryptophan alone reduced inflammation.
Nathan Goodyear

Administration route-dependent effects of estrogens on IGF-I levels during fixed GH rep... - 0 views

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    oral estrogen therapy decreased IGF-1 concentrations in those women taking growth hormone, requiring high dosing of HGH versus that in women using estrogen through a transdermal approach.
Nathan Goodyear

Regulation of muscle mass by growth hormone and IGF-I - 0 views

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    good review of GH and IGF-1 impact on muscle growth/muscle loss.
Nathan Goodyear

Insulin-like growth factor-I, its binding proteins (IGFBP-1 and IGFBP-3), and growth ho... - 0 views

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    GH, IGF-1, IGFBP-1, and IGFBP-3 were not found to be associated with increased risk of breast cancer in premenopuasal women.
Nathan Goodyear

http://www.diabetologia-journal.org/files/Narendran.pdf - 0 views

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    Exercise is not just for calories out.  Exercise increases growth hormone, IGF-1, glucagon-like peptide 1, IL-6, and IL-1ra.  The effect is to GH increases beta islet cell mass and protects beta cell lines against IL-1beta, Interferon-gamma and TNF-alhpa induced apoptosis.  IL-6 increased production increases GLP-1 and IL-1ra which counters IL-1beta.  Interleukin-1beta induces islet cell apoptosis and thus IL-1ra counters this pro-inflammatory signal.
Nathan Goodyear

Metformin in cancer prevention and therapy - 0 views

  • relative risks imparted by diabetes are greatest (about two fold or higher) for cancers of the liver, pancreas, and endometrium, and lesser (about 1.2-1.5 fold) for cancers of the colon and rectum, breast, and bladder
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    Metformin useful in the prevention of cancer, but also on the treatment as an adjunct.  Good review through possible mechanisms, mToR, insulin, IGF-1...
Nathan Goodyear

Regulation of production and secretion of sex hormone-binding globulin in HepG2 cell cu... - 0 views

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    SHBG and hormones.  Insulin, IGF-1, and EGF decrease SHBG levels.  Contrast that with estradiol, testosterone, T3, and cortisol that increase SHBG
Nathan Goodyear

Role of the growth hormone-IGF-1 axis in cancer: Expert Review of Endocrinology & Metab... - 0 views

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    Great read on the different mechanisms by which GH promotes carcinogenesis and growth via STATs, P13K/Akt, mTOR, IGF-1...
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