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Nathan Goodyear

Long-term effects of calorie restriction on serum sex hormone concentrations in men - 0 views

www.ncbi.nlm.nih.gov/...PMC3569090

calorie restriction Testosterone low T low Testosterone male hormones' nutrition diet

shared by Nathan Goodyear on 27 Sep 16 - No Cached
  • Nathan Goodyear on 27 Sep 16
     
    long term calorie restriction resulted in a decrease in total Testosterone and free Testosterone; an increase in SHBG was found.
Nathan Goodyear

Effect of Lifestyle Intervention on the Hormonal Profile of Frail, Obese Older Men. - P... - 0 views

www.ncbi.nlm.nih.gov/...26892583

lifestyle intervention low T low Testosterone Testosterone male hormones men hormones obesity estrogen

shared by Nathan Goodyear on 27 Sep 16 - No Cached
  • Nathan Goodyear on 27 Sep 16
     
    10% weight loss in older men, resulted in fat loss; this resulted in a decrease in estrogen production and an increase in Testosterone all via lifestyle interventions.
Nathan Goodyear

Testosterone therapy in hypogonadal men and potential prostate cancer risk: a systemati... - 0 views

www.ncbi.nlm.nih.gov/...PMH0027131

low T low Testosterone Testosterone testosterone therapy cancer prostate cancer male hormones

shared by Nathan Goodyear on 01 Oct 16 - No Cached
  • Nathan Goodyear on 01 Oct 16
     
    meta-analysis finds no evidence of testosterone therapy and increased risk of prostate cancer.
trungtamnamkhoa

Orthomol Fertil Plus - Nhà Thuốc Nam Khoa - Men's Health Pharmacy - 2 views

nhathuocnamkhoa.com/...-cho-nam-gioi-mong-muon-co-con

pharmacy men health healthy hormones cancer hormone Disease Male

shared by trungtamnamkhoa on 25 Jun 19 - No Cached
  • trungtamnamkhoa on 25 Jun 19
     
    Orthomol Fertil plus nâng cao chất lượng tinh trùng theo những tiêu chí: Khả năng chuyển động của tinh trùng, Mật độ tinh trùng, hình dạng thông thường của tinh trùng. Orthomol Fertil plus là sản phẩm bổ sung vitamin, khoáng vật, các yếu tố vi lượng nhu yếu cho nam giới. Được lớn mạnh dựa trên "Liệu pháp dinh dưỡng Orthomolecular" của tấn sĩ hóa sinh Linus Pauling (người hai lần đoạt giải Nobel 1954, 1962). Orthomol Natal - thương hiệu nổi tiếng của Đức. Các lưu ý giúp cải thiện chất lượng tinh trùng Nhiệt độ trong tinh hoàn luôn thấp hơn hai ° C so có nhiệt độ cơ thể. Nhiệt độ quá cao sở hữu thể ảnh hưởng đến giai đoạn sản xuất tinh trùng. Hạn chế khiến cho nóng ghế trong xe và mặc quần quá bó. Giữa hiện trạng thể chất và chất lượng tinh trùng của bạn với 1 sự ảnh hưởng lẫn nhau. Kể cách thức khác, ví như bạn khỏe mạnh, thì càng nâng cao thời cơ tinh trùng khỏe mạnh và đầy nhựa sống. lúc đạt cực khoái cổ tử cung tương trợ chuyên chở tinh trùng về phía dạ con. Do đó để thụ tinh thuận tiện thì người nữ giới phải đạt đỉnh sau người đàn ông và ko ngược lại.
trungtamnamkhoa

Penis enlargement due to where? Cause And Treatment - 1 views

trungtamnamkhoa.com/n-duong-vat-noi-mun-trang.html

penis pimples white acne male men health healthy cancer Testosterone hormone

shared by trungtamnamkhoa on 25 Jun 19 - No Cached
  • trungtamnamkhoa on 25 Jun 19
     
    The body of the white pimples is a common feature of boys entering puberty. Understanding their nature will help you no longer worry. White pimples on the penis and pores, squeezing out with a white core. Do these acne affect fertility? This top concern in many young people will be answered right after.
trungtamnamkhoa

Impact Of Unimaginable Harms Of Chickens Chicken Prevention - Men's Health Clinic - 1 views

trungtamnamkhoa.com/c-hai-cua-benh-sui-mao-ga.html

hormones cancer hormone Testosterone Men inflammation Disease Male HPV Viruss

shared by trungtamnamkhoa on 25 Jun 19 - No Cached
  • trungtamnamkhoa on 25 Jun 19
     
    The harmful effects of chicken papilloma disease not only stop at physical health but also the spirit of patients is seriously affected. Patients may be depressed, mentally in crisis when they know that they can follow them all their lives. Chicken ridge is considered the undeniable obsession of men. Referring to this disease, many boys are bored, because once they get sick, the chicken's neck often hangs and leaves many harms. Dr. Vo Duy Tam said, "The chicken's crest is a sexually transmitted disease caused by HPV (Human Papilloma Virus) - The virus causes human papilloma. Currently there are more than 130 HPV types that have been discovered, among them, the ones that often cause genital warts are types 6, 11, 16, and 18.
trungtamnamkhoa

Foreskin Sign Of What Disease? Treatment - 0 views

trungtamnamkhoa.com/-quy-dau-dau-hieu-benh-gi.html

hormones cancer hormone Testosterone inflammation Men Male Disease health healthy

shared by trungtamnamkhoa on 25 Jun 19 - No Cached
  • trungtamnamkhoa on 25 Jun 19
     
    Causes of itching For men, the cause of the itch can be divided into three groups: * The "little boy" hygiene is not right: Men - especially young people - often do not focus or "lazy" to clean the boy. This bad habit has gradually created an environment for the growth of genital fungi, causing an itching sensation. Besides, the selection of inappropriate cleaning solutions is also the reason that may be encountered in men. Some men reported using feminine cleaning solutions or shower gels to "bath" their "boy". This makes the itching condition more and more because the nature of the feminine hygiene solution is not suitable for his small skin, so it can easily lead to skin irritation, even leading to a disorder of the skin and creating favorable conditions for mushroom growth.
trungtamnamkhoa

Pimples In The Penis - What Is The Cause? - 1 views

trungtamnamkhoa.com/noi-mun-o-duong-vat.html

hormones cancer hormone Testosterone Men Health healthy Disease Male

shared by trungtamnamkhoa on 25 Jun 19 - No Cached
  • trungtamnamkhoa on 25 Jun 19
     
    The penis gets pimples, white or red items make men worried because they don't know the cause. In most of the causes of penile acne, the group of causes of sexually transmitted diseases is the most dangerous. Genital skin is very sensitive, especially in the penis. Only a small change can cause abnormal symptoms such as tumors, irritation, irritation and discomfort. Men need to understand the reasons for effective prevention and treatment. Group of allergy causes: Men with acne in the penis due to local allergies, for example, the penis skin has been exposed to "strange" substances from poor quality condoms. In addition, wearing underwear that is too tight, fabric material is not guaranteed or new clothes bought without washing well and many dust and dirt also cause irritation and penile pimples. Eating allergenic foods can also irritate the skin and, if unfortunately, the skin is as delicate as the "genital area".
Nathan Goodyear

Hypogonadism in the Aging Male Diagnosis, Potential Benefits, and Risks of Testosterone... - 0 views

www.ncbi.nlm.nih.gov/...PMC3312212

low T low Testosterone Testosterone Testosterone replacement therapy

shared by Nathan Goodyear on 07 May 17 - No Cached
  • Nathan Goodyear on 07 May 17
     
    Review of the literature on Low T, causes of low T, and associated symptoms.
Nathan Goodyear

A Validated Age-Related Normative Model for Male Total Testosterone Shows Increasing Va... - 0 views

www.ncbi.nlm.nih.gov/...PMC4190174

Testosterone low T low Testosterone

shared by Nathan Goodyear on 07 May 17 - No Cached
  • Nathan Goodyear on 07 May 17
     
    Interesting read: study finds peak Testosterone at age 19 in men; Testosterone decline was see up to age 40 at which decline was variable beyond age 40
  • Open TeleShop on 17 May 17
     
    Hey Dear Check Out Our Online Shopping store in all Over Pakistan.As Seen as On Tv Products Like as Health Beauty,Fitness,Homeware,Kitchenware,And Other Electronic Products in Pakistan Check Out Now| www.openTeleshop.Com
Nathan Goodyear

A Perspective on Middle-Aged and Older Men With Functional Hypogonadism: Focus on Holis... - 0 views

www.ncbi.nlm.nih.gov/...28359097

low T low Testosterone lifestyle intervention hypogonadism male hormones

shared by Nathan Goodyear on 27 Apr 17 - No Cached
  • Nathan Goodyear on 27 Apr 17
     
    literature review finds that lifestyle interventions can improve Testosterone levels in men.  For many men, low Testosterone, is the result not the cause.
  • Open TeleShop on 17 May 17
     
    Hey Dear Check Out Our Online Shopping store in all Over Pakistan.As Seen as On Tv Products Like as Health Beauty,Fitness,Homeware,Kitchenware,And Other Electronic Products in Pakistan Check Out Now| www.openTeleshop.Com
Nathan Goodyear

Dopamine and male sexual function. - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...11805404

dopamine ED erectile dysfunction erection

shared by Nathan Goodyear on 21 May 17 - No Cached
  • Nathan Goodyear on 21 May 17
     
    dopamine plays role in erections in men.
Nathan Goodyear

Treatment of Men for "Low Testosterone": A Systematic Review - 0 views

journals.plos.org/...article

low t low Testosterone Testosterone Testosterone therapy

shared by Nathan Goodyear on 11 Jan 17 - No Cached
  • Of 47 studies that assessed sexual function or satisfaction, 23 studies reported beneficial effects of testosterone treatment for at least 1 measure of sexual function or satisfaction,[6, 26, 35, 37, 40, 43–60] and 24 studies did not show testosterone-associated improvements in any sexual function endpoint
  • Of 31 studies that evaluated erectile function, 15 found no improvement with testosterone therapy
  • Twelve studies included men with ED; 8 found no benefit of testosterone over placebo
  • ...2 more annotations...
  • Of 23 studies that specifically reported changes in libido, 13 found that testosterone treatment increased libido,[26, 35, 37, 45, 46, 54, 56, 60, 63, 65, 70, 77, 79] eight found no effect,
  • Eleven studies used the Aging Males’ Symptoms scale, which includes 3 questions on libido and sexual function. Five studies found no difference between testosterone and placebo on total scores,[26, 54, 57, 72, 76] and 4 studies found a benefit of testosterone
  • Nathan Goodyear on 11 Jan 17
     
    A systemic review of Testosterone benefit in men stirs the pot.  I can't say that I agree with the majority of their conclusions.  What I do agree with them on is that the majority of men on Testosterone therapy likely don't need it and are simply using Testosterone as a drug.
Nathan Goodyear

Effects of chronic celecoxib on testicular function in normal and lipopolysaccharide-tr... - 0 views

www.ncbi.nlm.nih.gov/...18522674

low Testosterone Testosterone male hormones inflammation LPS lipopolysaccharides

shared by Nathan Goodyear on 13 Apr 17 - No Cached
  • Nathan Goodyear on 13 Apr 17
     
    Animal study from '09 found that COX2 inhibitor blunted LPS decrease in testes weight, decrease in testicular interstitial fluid, and serum Testosterone.  The point here is that LPS, in this animal model, decreased gonadal weight and Testosterone production and the anti inflammatory, COX2, blunted that effect.
Nathan Goodyear

The Risk of Fluoroquinolone-induced Tendinopathy and Tendon Rupture - 0 views

www.ncbi.nlm.nih.gov/...PMC2921747

flouroquinolones ciprofloxacin levoquin tendinitis tendinopathy Tendon rupture

shared by Nathan Goodyear on 02 Aug 17 - No Cached
  • Achilles tendinitis or rupture is among the most serious side effects associated with FQ use
  • The large body of data provided by clinical reports, histopathological examination, and experimental studies provides cogent evidence supporting a direct link between FQ use and tendonitis/tendon rupture
  • Risk factors associated with FQ-induced tendon disorders include age greater than 60 years, corticosteroid therapy, renal failure, diabetes mellitus, and a history of musculoskeletal disorders
  • ...17 more annotations...
  • The average age of FQ-induced tendinopathy is 64 years, with a male-to-female ratio of 2:1, and a 27-percent incidence of bilateral involvement
  • Although more than 95 percent of cases of tendinitis/rupture secondary to FQ involve the Achilles tendon, other reported sites of tendon involvement include the quadriceps, peroneus brevis, and rotator cuff
  • FQs demonstrate a 3.8-fold greater risk for development of Achilles tendinitis/rupture
  • a large population-based case control analysis, patients treated with FQs exhibited a substantially increased risk of developing tendon disorders overall (1.7-fold), tendon rupture (1.3-fold), and ATR (4.1-fold)
  • patients taking FQs with concurrent exposure to corticosteroids were found to experience a compounding effect on the risk of tendon rupture, specifically a 46-fold greater predisposition
  • Some authors have recommended that patients with a history of Achilles tendinitis and advanced age should not be prescribed FQ antibiotics
  • Approximately 50 percent of patients will recover within 30 days, with 25 percent of patients having symptoms persistent for longer than two months
  • The mean latency period between the start of FQ treatment and occurrence of tendinopathy has been reported to be a few hours to months, with a median onset of 6 days
  • The exact pathophysiology of FQ-induced tendinopathy remains elusive
  • it is possible that FQs have a direct cytotoxic effect on enzymes found in mammalian musculoskeletal tissue
  • It has been theorized that FQs disproportionately affect human tendons that have a limited capacity for repair, such as in older patients or structural compromise (i.e., pre-existing tendinopathy or trauma)
  • histopathological findings are similar to those observed in overuse conditions in athletes
  • Treatment with a FQ should be discontinued and physical therapy initiated
  • treatment should include rest and decreasing the physical load on the tendon.
  • Approximately 85 percent of patients present in less than one month
  • Because rupture can occur even late in the course of treatment or after discontinuation of FQ use, patients receiving a FQ should be counseled to seek medical attention immediately if symptoms, such as redness, pain, swelling, and stiffness, develop
  • FQs should be used cautiously in patients with risk factors associated with tendinitis, such as advanced age, history of tendon rupture, corticosteroid use, and/or acute or chronic renal dysfunction
  • Nathan Goodyear on 02 Aug 17
     
    Great review of the link between flouroquinolones and Tendinitis and Tendon rupture.  Yes, there is a direct link.
Nathan Goodyear

Efficacy and Safety of an Injectable Combination Hormonal Contraceptive for Men | The J... - 0 views

academic.oup.com/...jc.2016-2141

Testosterone contraception male contraception

shared by Nathan Goodyear on 22 Sep 17 - No Cached
  • Nathan Goodyear on 22 Sep 17
     
    Study finds injectable contraception in men leaves delayed suppressed LH and Testosterone. This drug design is by those devoid of overall knowledge of physiology. Lower Testosterone in men has significant negative metabolic effect, neurotransmitter impact, and what about epigenetics. Some men have epigenetically increased risk of hypogonadism. This contraception is a bad idea physiologically.
Nathan Goodyear

Late Disseminated Lyme Disease: Associated Pathology and Spirochete Persistence Post-Tr... - 0 views

ajp.amjpathol.org/...fulltext

Lyme Lyme disease borrelia burgdorferi

shared by Nathan Goodyear on 14 Dec 17 - No Cached
  • In this study, we have demonstrated microscopic pathology ranging from minimal to moderate in multiple different tissues previously reported to be involved with LD, including the nervous system (central and peripheral), heart, skeletal muscle, joint-associated tissues, and urinary bladder 12 to 13 months following tick-inoculation of rhesus macaques by Bb strain B31
  • Based on histomorphology, inflammation consisted predominantly of lymphocytes and plasma cells, with rare scattered histiocytes
  • in rare instances, morphologically intact spirochetes were observed in inflamed brain and heart tissue sections from doxycycline-treated animals
  • ...41 more annotations...
  • colocalization of the Bb 23S rRNA probe was not observed in any of the sections of experimental inoculated animals shown to harbor rare persistent spirochetes (Supplemental Figure S1). Previous in vitro work has shown large decreases in Bb rRNA levels when in a stationary phase of growth despite the majority of spirochetes remaining viable
  • The possibility that the spirochetes were intact but dead also exists, though this may be unlikely given the precedence for viable but non-cultivable B. burgdorferi post-treatment
  • The doxycycline dose utilized in this study (5mg/kg) was based on a previous pharmacokinetic analysis of oral doxycycline in rhesus macaques proven to be comparable to levels achieved in humans and was meant to mimic treatment of disseminated LD
  • In addition to the brain of two treated animals, rare morphologically intact spirochetes immunoreactive to OspA were observed in the heart of one treated animal
  • Although we did not measure the doxycycline levels in the cerebrospinal fluid, they have been found to be 12% to 15% of the amount measured in serum
  • We and others have demonstrated the development of a drug-tolerant persister population when B. burgdorferi are treated with antibiotics in vitro
  • The adoption of a dormant or slow-growing phenotype likely allows the spirochetes to survive and re-grow following removal of antibiotic
  • The basic premise that antibiotic tolerance may be an adaptation of the sophisticated stringent response required for the enzootic cycle by the spirochetes is described in a recent review as well
  • Although current IDSA guidelines recommend intravenous ceftriaxone (2g daily for 30 days) over oral doxycycline for treatment of neuroborreliosis, a randomized clinical trial failed to show any enhanced efficacy of I.V. penicillin G to oral doxycycline for treatment of Lyme neuroborreliosis (no treatment failures were reported in this study of 54 patients).
  • we can speculate that the minimal to moderate inflammation that was observed, especially within the CNS and PNS can, in part, explain the breadth of symptoms experienced by late stage Lyme disease patients, such as cognitive impairment and neuralgia.
  • Erythema migrans, the clinical hallmark of early localized Lyme disease, was observed in one of the rhesus macaques from this study.
  • In 2014, a trailblazing study in mice demonstrated a dramatic decline in B. burgdorferi DNA in the tissues for up to eight months after antibiotic treatment followed by the resurgence of B. burgdorferi growth 12 months after treatment
  • This study provides evidence that the slow-growing spirochetes which persist after treatment, but are not cultivable in standard growth media may remain viable.
  • The first well-documented indication of Lyme disease (LD) in the United States occurred in the early 1970s
  • Lyme, Connecticut.
  • Lyme disease is now known to be caused by multiple closely related genospecies classified within the Bb sensu lato complex, representing the most common tick-borne human disease in the Northern Hemisphere
  • approximately 30,000 physician-reported cases occur annually in the United States, the annual incidence has been estimated to be 10-fold higher by the Centers for Disease Control and Prevention.6
  • Current antibiotic therapy guidelines outlined by the Infectious Disease Society of America (IDSA) are successful in the treatment of LD for the majority of LD patients, especially when administered early in disease immediately following identification of erythema migrans (EM)
  • ‘post-treatment Lyme disease syndrome’ (PTLDS)
  • host-adapted spirochetes that persist in the tissues, probably in small numbers, inaccessible or impervious to antibiotic
  • inflammatory responses to residual antigens from dead organisms
  • residual tissue damage following pathogen clearance;
  • autoimmune responses, possibly elicited by antigenic mimicry
  • Experimental studies on immunocompetent mice, dogs, and rhesus macaques have provided evidence for the persistence of Bb spirochetes subsequent to antibiotic treatment in the form of residual spirochetes detected within tissue by IFA and PCR, and recovered by xenodiagnoses
  • Ten male rhesus macaques
  • half (five) of the NHP received antibiotic treatment, consisting of 5 mg/kg oral doxycycline twice per day.
  • Minimal and focal lymphoplasmacytic inflammation
  • inflammation was observed in the leptomeninges overlying a section of temporal cerebral cortex
  • Minimal localized lymphoplasmacytic choroiditis
  • Peripheral nerves contained minimal to moderate lymphoplasmacytic inflammation with a predilection for collagen-rich epineurium and perivascular spaces
  • Inflammation was observed in 56% (5/9) of the NHPs irrespective of treatment group
  • For all animals, inflammation was reserved to perineural tissue
  • The treatment lasted 28 days
  • Minimal to mild lymphoplasmacytic inflammation of either the myocardial interstitium (Figure 2Figure 2A), pericardium (Figure 2Figure 2B), or combination therein was observed in 60% of NHPs
  • A single morphologically intact spirochete, as indicated by positive red immunofluorescence (Figure 2Figure 2C), was observed in the myocardium of one treated animal
  • mild, multifocal lymphoplasmacytic inflammation was observed in one doxycycline-treated animal
  • three animals exhibited minimal to mild lymphoplasmacytic inflammation affecting joint-associated structures
  • 10% to -20% of human patients treated
  • Multiple randomized placebo-controlled studies which evaluated sustained antimicrobial therapy concluded that there is no benefit in alleviating patients’ symptoms and indicated that long-term antibiotic therapy may even be detrimental to patients due to potential associated complications (ie, catheter infection and/or clostridial colitis)
  • and the rapid clearance of dead spirochetes in a murine model
  • higher doses may be needed to combat neuroborreliosis
  • Nathan Goodyear on 14 Dec 17
     
    persistent borrelia burgdorferia were found in the brain (2) and the heart (1) up to 13 months post standard antibiotic treatment suggesting borrelia burdorferia, the cause of Lyme, can persist in a chronic, persistant state poste acute treatment.
Nathan Goodyear

Ibuprofen alters human testicular physiology to produce a state of compensated hypogona... - 0 views

www.pnas.org/...1715035115.full

ibuprofen Testosterone epigenetics hormones low Testosterone low T

shared by Nathan Goodyear on 09 Jan 18 - No Cached
  • The levels of LH in the ibuprofen group had increased by 23% after 14 d of administration
  • This increase was even more pronounced at 44 d, at 33%
  • We found an 18% decrease (P = 0.056) in the ibuprofen group compared with the placebo group after 14 d (Fig. 1A) and a 23% decrease (P = 0.02) after 44 d (Fig. 1C). Taken together, these in vivo data suggest that ibuprofen induced a state of compensated hypogonadism during the trial, which occurred as early as 14 d and was maintained until the end of the trial at 44 d
  • ...27 more annotations...
  • We first investigated testosterone production after 24 and 48 h of ibuprofen exposure to assess its effects on Leydig cell steroidogenesis. Inhibition of testosterone levels was significant and dose-dependent (β = −0.405, P = 0.01 at 24 h and β = −0.664, P < 0.0001 at 48 h) (Fig. 2A) and was augmented over time
  • The AMH data show that the hypogonadism affected not only Leydig cells but also Sertoli cells and also occurred as early as 14 d of administration
  • Sertoli cell activity showed that AMH levels decreased significantly with ibuprofen administration, by 9% (P = 0.02) after 14 d (Fig. 1B) and by 7% (P = 0.05) after 44 d compared with the placebo group
  • Examination of the effect of ibuprofen exposure on both the ∆4 and ∆5 steroid pathways (Fig. 2B) showed that it generally inhibited all steroids from pregnenolone down to testosterone and 17β-estradiol; the production of each steroid measured decreased at doses of 10−5–10−4 M. Under control conditions, production of androstenediol and dehydroepiandrosterone (DHEA) was below the limit of detection except in one experiment with DHEA
  • Measuring the mRNA expression of genes involved in steroidogenesis in vitro showed that ibuprofen had a profound inhibitory effect on the expression of these genes (Fig. 3 B–D), consistent with that seen above in our ex vivo organ model. Taken together, these data examining effects on the endocrine cells confirm that ibuprofen-induced changes in the transcriptional machinery were the likely reason for the inhibition of steroidogenesis.
  • Suppression of gene expression concerned the initial conversion of cholesterol to the final testosterone synthesis. Hence, expression of genes involved in cholesterol transport to the Leydig cell mitochondria was impaired
  • A previous study reported androsterone levels decreased by 63% among men receiving 400 mg of ibuprofen every 6 h for 4 wk
  • We next examined the gene expression involved in testicular steroidogenesis ex vivo and found that levels of expression of every gene that we studied except CYP19A1 decreased after exposure for 48 h compared with controls
  • the changes in gene expression indicate that the transcriptional machinery behind the endocrine action of Leydig cells was most likely impaired by ibuprofen exposure.
  • Together, these data show that ibuprofen also directly impairs Sertoli cell function ex vivo by inhibiting transcription
  • ibuprofen use in men led to (i) elevation of LH; (ii) a decreased testosterone/LH ratio and, to a lesser degree, a decreased inhibin B/FSH ratio; and (iii) a reduction in the levels of the Sertoli cell hormone AMH
  • The decrease in the free testosterone/LH ratio resulted primarily from the increased LH levels, revealing that testicular responsiveness to gonadotropins likely declined during the ibuprofen exposure. Our data from the ex vivo experiments support this notion, indicating that the observed elevation in LH resulted from ibuprofen’s direct antiandrogenic action
  • AMH levels were consistently suppressed by ibuprofen both in vivo and ex vivo, indicating that this hormone is uncoupled from gonadotropins in adult men. The ibuprofen suppression of AMH further demonstrated that the analgesic targeted not only the Leydig cells but also the Sertoli cells, a feature encountered not only in the human adult testis but also in the fetal testis
  • ibuprofen displayed broad transcription-repression abilities involving steroidogenesis, peptide hormones, and prostaglandin synthesis
  • a chemical compound, through its effects on the signaling compounds, can result in changes in the testis at gene level, resulting in perturbations at higher physiological levels in the adult human
  • The analgesics acetaminophen/paracetamol and ibuprofen have previously been shown to inhibit the postexercise response in muscles by repressing transcription
  • Previous ex vivo studies on adult testis have indeed pointed to an antiandrogenicity, only on Leydig cells, of phthalates (41), aspirin, indomethacin (42), and bisphenol A (BPA) and its analogs
  • ibuprofen’s effects were not restricted to Leydig and Sertoli cells, as data showed that the expression of genes in peritubular cells was also affected
  • short-term exposure
  • In the clinical setting, compromised Leydig cell function resulting in increased insensitivity to LH is defined as compensated hypogonadism (4), an entity associated with all-cause mortality
  • compensated hypogonadic men present with an increased likelihood of reproductive, cognitive, and physical symptoms
  • an inverse relationship was recently reported between endurance exercise training and male sexual libido
  • AMH concentrations are lower in seminal plasma from patients with azoospermia than from men with normal sperm levels
  • inhibin B is a key clinical marker of reproductive health (32). The function of AMH, also secreted by Sertoli cells, and its regulation through FSH remain unclear in men
  • the striking dual effect of ibuprofen observed here on both Leydig and Sertoli cells makes this NSAID the chemical compound, of all the chemical classes considered, with the broadest endocrine-disturbing properties identified so far in men.
  • after administration of 600 mg of ibuprofen to healthy volunteers
  • 14 d or at the last day of administration at 44 d
  • Nathan Goodyear on 09 Jan 18
     
    ibuprofen alters genetic expression that results in decreased Testosterone production.
Nathan Goodyear

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

www.ncbi.nlm.nih.gov/...PMC5864526

genomic signaling cancer hormones non-genomic signaling

shared by Nathan Goodyear on 10 Apr 21 - No Cached
  • 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
  • ...25 more annotations...
  • 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
      Nathan Goodyear on 10 Apr 21
       
      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
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