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https://www.readbyqxmd.com/read/28449232/safety-pharmacokinetics-and-pharmacologic-effects-of-the-selective-androgen-receptor-modulator-gsk2881078-in-healthy-men-and-postmenopausal-women
#1
Richard V Clark, Ann C Walker, Susan Andrews, Philip Turnbull, Jeffrey A Wald, Mindy H Magee
AIM: Selective androgen receptor modulators (SARMs) induce anabolic effects on muscle without the adverse effects of androgenic steroids. In this first-in-human study, we report safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of the SARM GSK2881078. METHODS: In Part A, healthy young men (n = 10) received a single dose of study drug (0 mg, 0.05 mg, 0.1 mg, 0.2 mg GSK2881078 or matching-placebo). In Part B, repeat-dose cohorts in men (n = 65) were 0...
April 27, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28448615/emphysema-is-associated-with-thoracic-vertebral-bone-attenuation-on-chest-ct-scan-in-hiv-infected-individuals
#2
Alycia Petraglia, Joseph K Leader, Matthew Gingo, Meghan Fitzpatrick, John Ries, Cathy Kessinger, Lorrie Lucht, Danielle Camp, Alison Morris, Jessica Bon
BACKGROUND: Age-related chronic diseases are prevalent in HIV-infected persons in the antiretroviral therapy (ART) era. Bone mineral density (BMD) loss and emphysema have separately been shown to occur at a younger age and with lesser risk exposure in HIV-infected compared to HIV-uninfected individuals. In non-HIV infected smokers, emphysema has been shown to independently predict low BMD. We hypothesized that emphysema would independently associate with thoracic vertebral bone attenuation, a surrogate for bone mineral density, in HIV-infected individuals...
2017: PloS One
https://www.readbyqxmd.com/read/28442349/perinatal-programming-of-the-orexinergic-hypocretinergic-system-in-hypothalamus-and-anterior-pituitary-by-testosterone
#3
Natalia I Cataldi, Victoria A Lux-Lantos, Carlos Libertun
Orexins A/B derived from hypothalamic prepro-orexin (PPO) are agonists for orexin receptors 1 (OX1) and 2 (OX2). Previously, we showed clear sex differences in the hypothalamic-pituitary-gonadal orexinergic system in adult rodents. Here, we studied the effect of sexual brain differentiation on the orexinergic system in neuroendocrine structures regulating reproduction. We evaluated: a: proestrous and neonatally androgenized female rats; b: adult males, untreated or gonadectomized in adulthood and injected with oil or estradiol and progesterone (E2/P4); c: control and demasculinized males (perinatally treated with flutamide and later castration) injected either with oil or E2/P4 in adulthood...
April 22, 2017: Peptides
https://www.readbyqxmd.com/read/28442274/sex-differences-in-exercise-efficacy-to-improve-cognition-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials-in-older-humans
#4
REVIEW
Cindy K Barha, Jennifer C Davis, Ryan S Falck, Lindsay S Nagamatsu, Teresa Liu-Ambrose
Exercise is a non-pharmacological strategy to mitigate the deleterious effects of aging on brain health. However, a large amount of variation exists in its efficacy. Sex of participants and exercise type are two possible factors contributing to this variation. To better understand this, we conducted a concurrent systematic review and meta-analysis of cognitively healthy older adults. Executive functions, episodic memory, visuospatial function, word fluency, processing speed and global cognitive function were examined for exercise- and sex-dependent effects...
April 22, 2017: Frontiers in Neuroendocrinology
https://www.readbyqxmd.com/read/28440542/menstrual-and-reproductive-factors-and-lung-cancer-risk-a-pooled-analysis-from-the-international-lung-cancer-consortium-ilcco
#5
Soumaya Ben Khedher, Monica Neri, Alexandra Papadopoulos, David C Christiani, Nancy Diao, Curtis C Harris, Susan Olivo-Marston, Ann G Schwartz, Michele Cote, Anita Koushik, Jack Siemiatycki, Maria Teresa Landi, Rayjean J Hung, John McLaughlin, Eric J Duell, Angeline S Andrew, Irene Orlow, Bernard J Park, Hermann Brenner, Kai-Uwe Saum, Angela C Pesatori, Isabelle Stücker
Many clinical features of lung cancer are different in women and men. Sex steroid hormones exert effects in non-reproductive organs, such as the lungs. The association between menstrual and childbearing factors and the risk of lung cancer among women is still debated. We performed a pooled analysis of eight studies contributing to the International Lung Cancer Consortium (ILCCO; 4,386 cases and 4,177 controls). Pooled associations between menstrual or reproductive factors and lung cancer were estimated using multivariable unconditional logistic regression...
April 25, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28438170/immunolocalization-of-steroidogenic-enzymes-in-the-vaginal-mucous-of-galea-spixii-during-the-estrous-cycle
#6
Amilton Cesar Dos Santos, Alan James Conley, Moacir Franco de Oliveira, Gleidson Benevides Oliveira, Diego Carvalho Viana, Antônio Chaves de Assis Neto
BACKGROUND: The synthesis of sex steroids is controlled by several enzymes such as17α-hydroxylase cytochrome P450 (P450c17) catalyzing androgen synthesis and aromatase cytochrome P450 (P450arom) catalyzing estrogen synthesis, both of which must complex with the redox partner NADPH-cytochrome P450 oxidoreductase (CPR) for activity. Previous studies have identified expression of steroidogenic enzymes in vaginal tissue, suggesting local sex steroid synthesis. The current studies investigate P450c17, P450aromatase and CPR expression in vaginal mucosa of Galea spixii (Spix cavy) by immuno-histochemical and western immunoblot analyses...
April 24, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28438051/similarity-of-female-central-hypogonadotropic-hypogonadism-and-postmenopause
#7
I Ilovayskaya, V Zektser, L Lazebnik
OBJECTIVES: Central (hypogonadotropic) hypogonadism in women could be a cause of persistent amenorrhea and hypoestrogenemia as observed in postmenopause. This study aimed to compare the clinical, hormonal and biochemical features in women with non-physiological (central hypogonadism) and physiological (postmenopause) hypoestrogenemia. METHODS: A total of 161 young women, median age 24.9 years (interquartile range (IQR) 21.2; 30.5) with central hypogonadism (with isolated hypogonadotropic hypogonadism, n = 76, and with hypopituitarism, n = 85), 53 healthy young women, median age 23...
April 24, 2017: Climacteric: the Journal of the International Menopause Society
https://www.readbyqxmd.com/read/28437784/the-physiology-of-childhood-growth-hormonal-regulation
#8
Emelie Benyi, Lars Sävendahl
The growth patterns of a child changes from uterine life until the end of puberty. Height velocity is highest in utero and declines after birth until puberty when it rises again. Important hormonal regulators of childhood growth are growth hormone, insulin-like growth factor 1, sex steroids, and thyroid hormone. This review gives an overview of these hormonal regulators of growth and their interplay with nutrition and other key players such as inflammatory cytokines.
April 24, 2017: Hormone Research in Pædiatrics
https://www.readbyqxmd.com/read/28436761/androgen-and-estrogen-shifts-in-men-before-and-after-bariatric-surgery-and-links-to-vitamins-and-trace-elements
#9
Alberto Rosenblatt, Joel Faintuch, Ivan Cecconello
Androgens and estrogens play a key role regarding sexual life and reproduction. Along with hypotestosteronemia, obese men exhibit a 2-fold increase in estradiol concentration, adversely infl uencing these parameters. Estrogens and adipokines also infl uence bone metabolism, exerting a direct effect on vitamin D, calcium homeostasis and bone health. Bariatric procedures normalize some sex hormones, and may reverse several obesity-related conditions. Estrogens levels may remain elevated postoperatively, and despite its protective effect on the skeleton, bariatric patients are more prone to fractures when compared to the general population...
April 24, 2017: International Journal for Vitamin and Nutrition Research. Journal International de Vitaminologie et de Nutrition
https://www.readbyqxmd.com/read/28431985/quercetin-interferes-with-the-fluid-volume-and-receptivity-development-of-the-uterus-in-rats-during-the-peri-implantation-period
#10
Huma Shahzad, Nelli Giribabu, Kamarulzaman Karim, Normadiah Kassim, Sekaran Muniandy, Kilari Eswar Kumar, Naguib Salleh
HYPOTHESIS: Quercetin could induce changes to the fluid volume and receptivity development of the uterus during peri-implantation period. METHODS: Female rats were treated with quercetin (10, 25 and 50mg/kg/day) subcutaneously beginning from day-1 pregnancy. Uterus was harvested at day-4 (following three days quercetin treatment) for morphological, ultra-structural, protein and mRNA expressional changes and plasma sex-steroid levels analyses. In another cohort of rats, implantation rate was determined at day-6 (following five days quercetin treatment)...
April 18, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28430630/estrogen-and-androgen-converting-enzymes-17%C3%AE-hydroxysteroid-dehydrogenase-and-their-involvement-in-cancer-with-a-special-focus-on-17%C3%AE-hydroxysteroid-dehydrogenase-type-1-2-and-breast-cancer
#11
REVIEW
Erik Hilborn, Olle Stål, Agneta Jansson
Sex steroid hormones such as estrogens and androgens are involved in the development and differentiation of the breast tissue. The activity and concentration of sex steroids is determined by the availability from the circulation, and on local conversion. This conversion is primarily mediated by aromatase, steroid sulfatase, and 17β-hydroxysteroid dehydrogenases. In postmenopausal women, this is the primary source of estrogens in the breast. Up to 70-80% of all breast cancers express the estrogen receptor-α, responsible for promoting the growth of the tissue...
February 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428343/mechanisms-of-autophagy-induction-by-sex-steroids-in-bovine-mammary-epithelial-cells
#12
Katarzyna Zielniok, Agnieszka Sobolewska, Malgorzata Gajewska
In dairy cattle mammary gland involution serves to remodel the secretory tissue, and occurs in a period of overlap between mammogenic stimulation caused by next developing pregnancy and tissue regression induced by milk stasis. At this time high concentrations of 17β-estradiol (E2) and progesterone (P4) support regeneration of the mammary tissue, as well as enhance autophagy, a cellular process induced in response to stressful conditions for energy generation and homeostasis maintenance. This study aimed to elucidate the mechanisms of autophagy induction by E2 and P4 using an in vitro model of involution based on 20-fold reduction of FBS content (from 10% to 0...
April 20, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28426945/testosterone-levels-in-healthy-men-correlate-negatively-with-serotonin-4-receptor-binding
#13
Erik Perfalk, Sofi da Cunha-Bang, Klaus K Holst, Sune Keller, Claus Svarer, Gitte M Knudsen, Vibe G Frokjaer
The serotonergic system integrates sex steroid information and plays a central role in mood and stress regulation, cognition, appetite and sleep. This interplay may be critical for likelihood of developing depressive episodes, at least in a subgroup of sensitive individuals. The serotonin 4 receptor (5-HT4R) indexes central serotonergic tonus, which may be related to endogenous sex-steroid levels in the mentally healthy state even though this remains elusive. Here we evaluate if peripheral levels of estradiol and testosterone are associated with 5-HT4R binding as imaged by [(11)C]SB207145 positron emission tomography in a group of 41 healthy men...
March 22, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28424375/mitochondria-a-central-target-for-sex-differences-in-pathologies
#14
REVIEW
Renée Ventura-Clapier, Maryline Moulin, Jérôme Piquereau, Christophe Lemaire, Mathias Mericskay, Vladimir Veksler, Anne Garnier
It is increasingly acknowledged that a sex and gender specificity affects the occurrence, development, and consequence of a plethora of pathologies. Mitochondria are considered as the powerhouse of the cell because they produce the majority of energy-rich phosphate bonds in the form of adenosine tri-phosphate (ATP) but they also participate in many other functions like steroid hormone synthesis, reactive oxygen species (ROS) production, ionic regulation, and cell death. Adequate cellular energy supply and survival depend on mitochondrial life cycle, a process involving mitochondrial biogenesis, dynamics, and quality control via mitophagy...
May 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28423352/prospective-serum-metabolomic-profile-of-prostate-cancer-by-size-and-extent-of-primary-tumor
#15
Jiaqi Huang, Alison M Mondul, Stephanie J Weinstein, Edward D Karoly, Joshua N Sampson, Demetrius Albanes
Two recent investigations found serum lipid and energy metabolites related to aggressive prostate cancer up to 20 years prior to diagnosis. To elucidate whether those metabolomic profiles represent etiologic or tumor biomarker signals, we prospectively examined serum metabolites of prostate cancer cases by size and extent of primary tumors in a nested case-control analysis in the ATBC Study cohort that compared cases diagnosed with T2 (n = 71), T3 (n = 51), or T4 (n = 15) disease to controls (n = 200). Time from fasting serum collection to diagnosis averaged 10 years (range 1-20)...
April 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420867/interaction-effects-of-polyfluoroalkyl-substances-and-sex-steroid-hormones-on-asthma-among-children
#16
Yang Zhou, Li-Wen Hu, Zhengmin Min Qian, Sarah Dee Geiger, Katelyn L Parrish, Shyamali C Dharmage, Brittany Campbell, Marjut Roponen, Pasi Jalava, Maija-Riitta Hirvonen, Joachim Heinrich, Xiao-Wen Zeng, Bo-Yi Yang, Xiao-Di Qin, Yungling Leo Lee, Guang-Hui Dong
To evaluate the interactions between polyfluoroalkyl substances (PFASs) and reproductive hormones and associated asthma, a total of 231 asthmatic and 225 non-asthmatic adolescents were selected from northern Taiwan in the Genetic and Biomarkers study for Childhood Asthma from 2009-2010. The interaction between PFASs and reproductive hormones on asthma was analyzed with a two-level binary logistic regression model. The results showed that, among asthmatics, PFASs were positively associated with estradiol levels and negatively associated with testosterone levels...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28419243/the-efficacy-and-safety-of-pubertal-induction-using-17beta-estradiol-in-transgirls
#17
Sabine E Hannema, Sebastian E E Schagen, Peggy T Cohen-Kettenis, Henriette A Delemarre-van de Waal
Introduction.: Puberty suppression using GnRH agonists, followed by induction of desired sex characteristics using sex steroids, is recommended by current guidelines as the treatment of choice for gender dysphoric adolescents although little evidence is available. Aim.: To evaluate the efficacy and safety of estrogen treatment for pubertal induction in transgirls (female-identifying adolescents assigned male at birth). Methods.: 28 Adolescents treated with oral estrogen for at least 1 year were included...
April 14, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28416813/brain-derived-neurotrophic-factor-val-66-met-genotype-and-ovarian-steroids-interactively-modulate-working-memory-related-hippocampal-function-in-women-a-multimodal-neuroimaging-study
#18
S-M Wei, E B Baller, P D Kohn, J S Kippenhan, B Kolachana, S J Soldin, D R Rubinow, P J Schmidt, K F Berman
Preclinical evidence suggests that the actions of ovarian steroid hormones and brain-derived neurotrophic factor (BDNF) are highly convergent on brain function. Studies in humanized mice document an interaction between estrus cycle-related changes in estradiol secretion and BDNF Val(66)Met genotype on measures of hippocampal function and anxiety-like behavior. We believe our multimodal imaging data provide the first demonstration in women that the effects of the BDNF Val/Met polymorphism on hippocampal function are selectively modulated by estradiol...
April 18, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28416614/modeling-combined-immunosuppressive-and-anti-inflammatory-effects-of-dexamethasone-and-naproxen-in-rats-predicts-the-steroid-sparing-potential-of-naproxen
#19
Xiaonan Li, Debra C DuBois, Dawei Song, Richard R Almon, William J Jusko, Xijing Chen
Dexamethasone (DEX), a widely prescribed corticosteroid (CS), has long been the cornerstone for the treatment of inflammation and immunological dysfunctions in Rheumatoid Arthritis (RA). The CS are frequently used in combination with other anti-rheumatic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs) to mitigate disease symptoms and minimize unwanted effects. The steroid dose-sparing potential of the NSAID naproxen (NPX) was explored with in vitro and in vivo studies...
April 17, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28413964/sex-genetic-interaction-in-the-risk-for-cerebrovascular-disease
#20
Donatella Pastore, Francesca Pacifici, Barbara Capuani, Raffaele Palmirotta, Chuanhui Dong, Andrea Coppola, Pasquale Abete, Mario Roselli, Paolo Sbraccia, Fiorella Guadagni, Davide Lauro, Tatjana Rundek, David Della-Morte
Cerebrovascular disease (CeVD) is one of the major cause of death and a leading cause of disability worldwide. CeVD is a complex and multifactorial disease caused by the interaction of environment and genetic factors. Women have lower CeVD incidence than men until an advanced age, when the incidence of CeVD rises dramatically in women. Therefore, sex has been validated as an important risk factor in the etiology of CeVD, especially ischemic stroke. Although the importance of sex steroids have been heavily studied in the mechanism of neuronal injury, the experimental and clinical data suggest that hormones do not fully account for male versus female CeVD patterns...
April 17, 2017: Current Medicinal Chemistry
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