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Nathan Goodyear

Gender and sex hormones in multiple sclerosis pathology and therapy - 0 views

  • It is now well recognized that the disease manifestation is reduced in pregnant women with relapsing-remitting MS
  • This occurs particularly during the third trimester when levels of estrogens (estradiol and estriol) and progesterone (see Table 2) are elevated up to about 20 times
  • This seems well correlated with a decrease in active white matter lesions detected by MRI
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  • This clinical improvement is however followed by temporary rebound exacerbations at post-partum, when the hormone levels decline
  • a shift from Th1 to Th2 immune response, expansion of suppressive regulatory T lymphocytes and decrease in the number of circulating CD16+ natural killer (NK)-cells
  • Th1 lymphocytes secrete proinflammatory cytokines (e.g. IL-2, IFNgamma, lymphotoxin) while Th2 cells secrete anti-inflammatory cytokines (e.g. IL-4, IL-5, IL-10), which favor humoral-mediated responses
  • Th2 cytokines are associated with down-regulation of Th1 cytokines and this Th2 shift is believed to provide protection from allograft rejection during pregnancy as well as from Th1-mediated autoimmune disease
  • it is worth noting that the levels of other hormones with anti-inflammatory activity (1,25-dihydroxy-vitamin D3, norepinephrine, cortisol) also increase by 2 to 4 times during late pregnancy
  • 1,25-dihydroxy vitamin D3 induces regulatory T-cell function important for development of self-tolerance
  • breast-feeding does not alter the relapse rate in women with MS
  • Leptin is a pleiotropic hormone produced primarily by adipocytes but also by T lymphocytes and neurons
  • Several lines of evidence indicate that leptin contributes to EAE/MS pathogenesis, influencing its onset and clinical severity, by acting as a proinflammatory cytokine which promotes regulatory T cell (Treg) anergy and hyporesponsiveness, resulting in increased Th1 (TNFalpha, INFgamma) and reduced Th2 (IL-4) cytokine production
  • circulating leptin levels are increased in relapsing-remitting MS patients (men and women analyzed together) while the CD4+CD25+Treg population decreases
  • As the leptin plasma concentrations are proportional to the amount of fat tissue, obese/overweight individuals produce higher levels of leptin
  • Nielsen et al found that estradiol and progesterone exert neuroprotection against glutamate neurotoxicity, while MPA antagonizes the neuroprotective effect of estradiol and exacerbated neuron death induced by glutamate excitotoxicity
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    very good review of the differences in MS and hormones between the sexes.
Nathan Goodyear

Redefining Metabolic Syndrome in Men (July 2012) Townsend Letter for Doctors & Patients - 0 views

  • Approximately 95% to 98% of testosterone is bound to a carrier protein at any given time, leaving just the remaining 2% to 5% as completely unbound and available for tissues to use
  • most serum laboratories offer a free testosterone level, which is a calculated value based on SHBG levels or determined with equilibrium dialysis
  • the hormone enters the salivary gland by passive diffusion
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  • Testosterone has a known age-related decline, and total levels typically drop by approximately 1.6% per year beginning for most men in their 30s
  • As estrogen levels rise, they prompt the body to produce more SHBG, which in turn has a higher binding affinity for testosterone, and drives the unbound fraction of the testosterone pool down even further
  • When the increase in SHBG is taken into account, the age-related decline in the level of hormone that can be used by the body is closer to 2% to 3% per year.
  • Stinging nettle (Urtica dioica), an herb commonly used for allergies, can also be employed to bind to SHBG, which leaves more testosterone available to tissues
  • Leptin, an adipose-derived peptide hormone that regulates appetite and metabolism, has been shown to directly inhibit testosterone production in animal models
  • tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) further inhibit Leydig cell testosterone production
  • Natural aromatase inhibitors include the bioflavonoids chrysin and luteolin
  • Zinc deficiency causes an upregulation of the aromatase enzyme
  • Testosterone reduces lipoprotein lipase (LPL) activity
  • there are several herbs that can work to boost testosterone levels, including longjack (Eurycoma longifolia), horny goat weed (Epimedium grandiflorum), and tribulus (Tribulus terrestris).
  • the majority of the hormone is bound to carrier proteins including sex hormone binding globulin (SHBG) and albumin
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    nice and short review on testosterone and men's  health.
Nathan Goodyear

Rapid determination of natural steroidal hormones in saliva for the clinical diagnoses - 0 views

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    This study looked at combined sex hormone analysis via gas chromatography-mass spec.  Levels were able to be detected as low as 0.002 mcro/L in saliva.  This study validates the GC-MS for the use of multiple, simultaneous steroid hormone analysis
Nathan Goodyear

Salivary Hormone Measurement Using LC/MS/MS: Specific and Patient- Friendly Tool for Assessment of Endocrine Function - 0 views

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    Great review on the literature of LC-MS/MS and now the new ESI-MS/MS method in saliva hormone testing. This technique is highly sensitive and specific. This article goes through the literature support for each hormone. It also discusses how/why saliva testing is valid. Conclusion: "the author believes that the saliva-based hormone test will be integrated into clinical practice in the near future".
Nathan Goodyear

Are serum hormones associated with the risk of prostate cancer? Prospective results from the Massachusetts Male Aging Study - 0 views

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    No correlation seen between serum hormones and prostate cancer risk.  Serum evaluation of hormones provides little, if any, clinically, relevant information.  The only association was found with a DHT metabolite--androstanediol.
Nathan Goodyear

JAMA Network | JAMA Dermatology | Sex Hormones and the Genesis of Autoimmunity - 0 views

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    Hormones and autoimmune disease.  This article specifically touches on SLE.  Good discussion on the biochemical signaling of hormones and their contribution to the increased autoimmunity found in women.
Nathan Goodyear

JAMA Network | JAMA | Estrogen Plus Progestin and the Incidence of Dementia and Mild Cognitive Impairment in Postmenopausal Women:  The Women's Health Initiative Memory Study: A Randomized Controlled Trial - 0 views

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    Estrogen with progestin worsens cognitive decline in women >65.  Little can be taken from this study other than, medroxyprogesterone acetate is a bad drug and should not be given to women for any purpose, especially in those >65.  One wonders if bioidentical, physiologic hormone replacement would have the same effect?  I doubt it.  The likely negative impact of hormones on the brain in women >65 is due to the negative effects of MPA, the change in inflammatory cytokines, and the change in receptors.
Nathan Goodyear

Minireview: Thyroid Hormone Transporters: The Knowns and the Unknowns: Molecular Endocrinology: Vol 25, No 1 - 0 views

  • the majority of TRs is located in the nucleus
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    thyroid hormone transportation.  The majority of the thyroid hormone receptors are in the nucleus of the cell.
Nathan Goodyear

Percutaneous progesterone delivery via cream or gel application in postmenopausal women: a randomized cross-over study of progesterone levels in serum, whole blood, saliva, and capillary blood. - 0 views

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    Topical hormones best evaluated via saliva and/or blood spot. Urine and particularly serum does not increase with dosing.  That does not mean the topical hormone therapy is ineffective, just that serum and urine are not optimal to follow topical therapy.  When looking at endogenous hormones without any therapies: serum, saliva, urine, and blood spot are equivalent.
Nathan Goodyear

Age-related hormonal adaptations, muscle circumference and strength development with 8weeks moderate intensity resistance training. - 0 views

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    Moderate resistance training program over 8 weeks associated with increased Testosterone production in young and middle age lean men.  Growth hormone was also increased in both groups.  ACTH and cortisol decreased in this lean men.  
Nathan Goodyear

Minireview: Cracking the Metabolic Code for Thyroid Hormone Signaling - 0 views

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    Here is a great review of thyroid hormone metabolism published in the very relevant journal Endocrinology.  The review describes the peripheral metabolism of the pro hormone T4 and the peripheral metabolism to free T3 and/or reverse T3 and the associated metabolic implications.  Why don't more endocrinologists read?This is an animal study.
Nathan Goodyear

Cellular and Molecular Basis of Deiodinase-Regulated Thyroid Hormone Signaling - 0 views

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    Anything and everything one would want to know regarding thyroid hormone signaling.  Doctors, especially endocrinologists, need to read this.  T4 is not or is ever inside target cells.  The enzymes, deiodinase types 1, 2, and 3, are what control the thyroid hormone at the cellular levels.  Deiodinase-2 is what generates T3 in the cytosol of the cell.  In contrast, deiodinase-3 is what generates rT3 which is inactive.  High Fat diet increases deiodinase-3.
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

Sex Hormone-Binding Globulin in the Diagnosis of Peripheral Tissue Resistance to Thyroid Hormone: The Value of Changes after Short Term Triiodothyronine Administration - 0 views

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    T3, and T4 for that matter, increases SHBG.  This would be a novel method to determine thyroid hormone receptor insensitivity or resistance.
Nathan Goodyear

Testosterone: a metabolic hormone in health and disease - 0 views

  • E2 and the inflammatory adipocytokines tumour necrosis factor α (TNFα) and interleukin 6 (IL6) inhibit hypothalamic production of GNRH and subsequent release of LH and FSH from the pituitary
  • Leptin, an adipose-derived hormone with a well-known role in regulation of body weight and food intake, also induces LH release under normal conditions via stimulation of hypothalamic GNRH neurons
  • In human obesity, whereby adipocytes are producing elevated amounts of leptin, the hypothalamic–pituitary axis becomes leptin resistant
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  • there is evidence from animal studies that leptin resistance, inflammation and oestrogens inhibit neuronal release of kisspeptin
  • Beyond hypothalamic action, leptin also directly inhibits the stimulatory action of gonadotrophins on the Leydig cells of the testis to decrease testosterone production; therefore, elevated leptin levels in obesity may further diminish androgen status
  • Prostate cancer patients with pre-existing T2DM show a further deterioration of insulin resistance and worsening of diabetic control following ADT
  • ADT for the treatment of prostatic carcinoma in some large epidemiological studies has been shown to be associated with an increased risk of developing MetS and T2DM
  • Non-diabetic men undergoing androgen ablation show increased occurrence of new-onset diabetes and demonstrate elevated insulin levels and worsening glycaemic control
  • increasing insulin resistance assessed by glucose tolerence test and hypoglycemic clamp was shown to be associated with a decrease in Leydig cell testosterone secretion in men
  • The response to testosterone replacement of insulin sensitivity is in part dependent on the androgen receptor (AR)
  • Low levels of testosterone have been associated with an atherogenic lipoprotein profile, characterised by high LDL and triglyceride levels
  • a positive correlation between serum testosterone and HDL has been reported in both healthy and diabetic men
  • up to 70% of the body's insulin sensitivity is accounted for by muscle
  • Testosterone deficiency is associated with a decrease in lean body mass
  • relative muscle mass is inversely associated with insulin resistance and pre-diabetes
  • GLUT4 and IRS1 were up-regulated in cultured adipocytes and skeletal muscle cells following testosterone treatment at low dose and short-time incubations
  • local conversion of testosterone to DHT and activation of AR may be important for glucose uptake
  • inverse correlation between testosterone levels and adverse mitochondrial function
  • orchidectomy of male Wistar rats and associated testosterone deficiency induced increased absorption of glucose from the intestine
  • (Kelley & Mandarino 2000). Frederiksen et al. (2012a) recently demonstrated that testosterone may influence components of metabolic flexibility as 6 months of transdermal testosterone treatment in aging men with low–normal bioavailable testosterone levels increased lipid oxidation and decreased glucose oxidation during the fasting state.
  • Decreased lipid oxidation coupled with diet-induced chronic FA elevation is linked to increased accumulation of myocellular lipid, in particular diacylglycerol and/or ceramide in myocytes
  • In the Chang human adult liver cell line, insulin receptor mRNA expression was significantly increased following exposure to testosterone
  • Testosterone deprivation via castration of male rats led to decreased expression of Glut4 in liver tissue, as well as adipose and muscle
  • oestrogen was found to increase the expression of insulin receptors in insulin-resistant HepG2 human liver cell line
  • FFA decrease hepatic insulin binding and extraction, increase hepatic gluconeogenesis and increase hepatic insulin resistance.
  • Only one, albeit large-scale, population-based cross-sectional study reports an association between low serum testosterone concentrations and hepatic steatosis in men (Völzke et al. 2010)
  • This suggests that testosterone may confer some of its beneficial effects on hepatic lipid metabolism via conversion to E2 and subsequent activation of ERα.
  • hypogonadal men exhibiting a reduced lean body mass and an increased fat mass, abdominal or central obesity
  • visceral adipose tissue was inversely correlated with bioavailable testosterone
  • there was no change in visceral fat mass in aged men with low testosterone levels following 6 months of transdermal TRT, yet subcutaneous fat mass was significantly reduced in both the thigh and the abdominal areas when analysed by MRI (Frederiksen et al. 2012b)
  • ADT of prostate cancer patients increased both visceral and subcutaneous abdominal fat in a 12-month prospective observational study (Hamilton et al. 2011)
  • Catecholamines are the major lipolysis regulating hormones in man and regulate adipocyte lipolysis through activation of adenylate cyclase to produce cAMP
  • deficiency of androgen action decreases lipolysis and is primarily responsible for the induction of obesity (Yanase et al. 2008)
  • may be some regional differences in the action of testosterone on subcutaneous and visceral adipose function
  • proinflammatory adipocytokines IL1, IL6 and TNFα are increased in obesity with a downstream effect that stimulates liver production of CRP
  • observational evidence suggests that IL1β, IL6, TNFα and CRP are inversely associated with serum testosterone levels in patients
  • TRT has been reported to significantly reduce these proinflammatory mediators
  • This suggests a role for AR in the metabolic actions of testosterone on fat accumulation and adipose tissue inflammatory response
  • testosterone treatment may have beneficial effects on preventing the pathogenesis of obesity by inhibiting adipogenesis, decreasing triglyceride uptake and storage, increasing lipolysis, influencing lipoprotein content and function and may directly reduce fat mass and increase muscle mass
  • Early interventional studies suggest that TRT in hypogonadal men with T2DM and/or MetS has beneficial effects on lipids, adiposity and parameters of insulin sensitivity and glucose control
  • Evidence that whole-body insulin sensitivity is reduced in testosterone deficiency and increases with testosterone replacement supports a key role of this hormone in glucose and lipid metabolism
  • Impaired insulin sensitivity in these three tissues is characterised by defects in insulin-stimulated glucose transport activity, in particular into skeletal muscle, impaired insulin-mediated inhibition of hepatic glucose production and stimulation of glycogen synthesis in liver, and a reduced ability of insulin to inhibit lipolysis in adipose tissue
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    Great review of the Hypogonadal-obesity-adipocytokine hypothesis.
Nathan Goodyear

JCI - Thyroid hormone resistance syndrome. Inhibition of normal receptor function by mutant thyroid hormone receptors. - 0 views

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    Thyroid hormone resistance is not a new term.  This study goes back to 1991.
Nathan Goodyear

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

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    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

ScienceDirect.com - Cell Metabolism - Estrogen Receptors and the Metabolic Network - 0 views

  • The pro-opiomelanocortin (POMC) neurons have an anorexigenic action and, when activated, reduce food intake through the release of two peptides, α-melanocyte-stimulating hormone (α-MSH) and cocaine-and-amphetamine-regulated transcripts (CART). The neuropeptide Y (NPY) neurons, on the other hand, release NPY hormone and agouti gene-related protein (AgRP), which prevent the binding of α-MSH to MC3R and MC4R, increasing food intake
  • This suggests that the central anorexic effects of E2 may occur via ERβ
  • The main hypothalamic areas involved in food intake and satiety are the arcuate nucleus (ARC), the lateral hypothalamus (LH), the paraventricular nucleus (PVN), the ventromedial hypothalamus (VMH), and the dorsomedial hypothalamus (DMH)
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  • Leptin is a potent anorexigenic and catabolic hormone secreted by adipose cells that reduces food intake and increases energy expenditure
  • E2 not only modulates leptin receptor mRNA in the ARC and VMH, but also increases hypothalamic sensitivity to leptin, altering peripheral fat distribution
  • ghrelin. It acts on growth hormone secretagogue receptors (GHSR1a) located in the ARC and is a potent stimulator of food intake
  • It thus appears that of the two ERs, ERα plays a predominant role in the CNS regulation of lipid and carbohydrate homeostasis.
  • Both ERs have been identified in the ARC
  • Stimulation of MCH neurons increases food intake and fat accumulation while its inhibition leads to decreased food intake and reduced fat accumulation.
  • Both ERs have been identified in the LH
  • both ERs have been identified in this nucleus
  • The PVN is the region of the hypothalamus with the highest expression of ERβ and is reported to be weakly ERα positive
  • The VMH is ERα regulated
  • Skeletal muscle is responsible for 75% of the insulin-induced glucose uptake in the body
  • GLUT4 is highly expressed in muscle and represents a rate-limiting step in the insulin-induced glucose uptake
  • data suggest that in the physiological range, E2 is beneficial for insulin sensitivity, whereas hypo- or hyperestrogenism is related to insulin resistance
  • In aging female rats, E2 treatment improves glucose homeostasis mainly through its ability to increase muscle GLUT4 content on the cell membrane
  • It is evident that ERα and ERβ have distinct actions and that much more research is needed to clearly identify the function of each receptor in muscle.
  • E2 prevents accumulation of visceral fat, increases central sensitivity to leptin, increases the expression of insulin receptors in adipocytes, and decreases the lipogenic activity of lipoprotein lipase in adipose tissue
  • In rats, ovariectomy increases body weight, intra-abdominal fat, fasting glucose and insulin levels, and insulin resistance followed by decreased phosphorylation of AMPK and its substrate acetyl-CoA carboxylase in adipose tissue
  • decreased adiponectin, PPARγ coactivator-1α (PGC-1α), and uncoupling protein 2 (UCP2) and increased resistin
  • Men with aromatase deficiency have truncal obesity, elevated blood lipids, and severe insulin resistance
  • Although not all studies are in agreement, polymorphisms of ERα in humans have been associated with risk factors for CVDs
  • Human subcutaneous and visceral adipose tissues express both ERα and ERβ, whereas only ERα mRNA has been identified in brown adipose tissue
  • suggesting that ERα is the main regulator of GLUT4 expression in adipose tissue
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    very nice article that looks at the balance of ER-alpha/ER-beta and their role in metabolic syndrome.  This article discusses the balance of  these receptors are tissue dependent in their effect.  I like their conclusion: "...but these mechanisms will never be completely understood if they are not considered in the context of a whole system.
Nathan Goodyear

Steroid Analysis in Saliva: An overview - 0 views

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    No test is perfect. This study analyzes problems with saliva hormone testing.  The authors of this study found saliva testing optimal for cortisol and less so for sex hormones.  Other studies have contradicted this conclusion.
Nathan Goodyear

Adrenal and gonadal steroid hormone deficiency in the pathogenesis of rheumatoid arthritis. - PubMed - NCBI - 0 views

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    Only abstract available here.  Low adrenal hormone output and low sex hormone production associated with increase RA.  Causation not proved here.
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