Browsing by Subject "Androgens"

Now showing 1 - 6 of 6
  • Thumbnail Image
    Item
    Benefits of Airway Androgen Receptor Expression in Human Asthma
    (American Thoracic Society, 2021) Zein, Joe G.; McManus, Jeffrey M.; Sharifi, Nima; Erzurum, Serpil C.; Marozkina, Nadzeya; Lahm, Timothy; Giddings, Olivia; Davis, Michael D.; DeBoer, Mark D.; Comhair, Suzy A.; Bazeley, Peter; Kim, Hyun Jo; Busse, William; Calhoun, William; Castro, Mario; Chung, Kian Fan; Fahy, John V.; Israel, Elliot; Jarjour, Nizar N.; Levy, Bruce D.; Mauger, David T.; Moore, Wendy C.; Ortega, Victor E.; Peters, Michael; Bleecker, Eugene R.; Meyers, Deborah A.; Zhao, Yi; Wenzel, Sally E.; Gaston, Benjamin; Biostatistics, School of Public Health
    Rationale: Androgens are potentially beneficial in asthma, but AR (androgen receptor) has not been studied in human airways. Objectives: To measure whether AR and its ligands are associated with human asthma outcomes. Methods: We compared the effects of AR expression on lung function, symptom scores, and fractional exhaled nitric oxide (FeNO) in adults enrolled in SARP (Severe Asthma Research Program). The impact of sex and of androgens on asthma outcomes was also evaluated in the SARP with validation studies in the Cleveland Clinic Health System and the NHANES (U.S. National Health and Nutrition Examination Survey).Measurements and Main Results: In SARP (n = 128), AR gene expression from bronchoscopic epithelial brushings was positively associated with both FEV1/FVC ratio (R2 = 0.135, P = 0.0002) and the total Asthma Quality of Life Questionnaire score (R2 = 0.056, P = 0.016) and was negatively associated with FeNO (R2 = 0.178, P = 9.8 × 10-6) and NOS2 (nitric oxide synthase gene) expression (R2 = 0.281, P = 1.2 × 10-10). In SARP (n = 1,659), the Cleveland Clinic Health System (n = 32,527), and the NHANES (n = 2,629), women had more asthma exacerbations and emergency department visits than men. The levels of the AR ligand precursor dehydroepiandrosterone sulfate correlated positively with the FEV1 in both women and men. Conclusions: Higher bronchial AR expression and higher androgen levels are associated with better lung function, fewer symptoms, and a lower FeNO in human asthma. The role of androgens should be considered in asthma management.
  • Thumbnail Image
    Item
    HSD3B1 genotype identifies glucocorticoid responsiveness in severe asthma
    (National Academy of Sciences, 2020-01-28) Zein, Joe; Gaston, Benjamin; Bazeley, Peter; DeBoer, Mark D.; Igo, Robert P., Jr; Bleecker, Eugene R.; Meyers, Deborah; Comhair, Suzy; Marozkina, Nadzeya V.; Cotton, Calvin; Patel, Mona; Alyamani, Mohammad; Xu, Weiling; Busse, William W.; Calhoun, William J.; Ortega, Victor; Hawkins, Gregory A.; Castro, Mario; Chung, Kian Fan; Fahy, John V.; Fitzpatrick, Anne M.; Israel, Elliot; Jarjour, Nizar N.; Levy, Bruce; Mauger, David T.; Moore, Wendy C.; Noel, Patricia; Peters, Stephen P.; Teague, W. Gerald; Wenzel, Sally E.; Erzurum, Serpil C.; Sharifi, Nima; Medicine, School of Medicine
    Asthma resistance to glucocorticoid treatment is a major health problem with unclear etiology. Glucocorticoids inhibit adrenal androgen production. However, androgens have potential benefits in asthma. HSD3B1 encodes for 3β-hydroxysteroid dehydrogenase-1 (3β-HSD1), which catalyzes peripheral conversion from adrenal dehydroepiandrosterone (DHEA) to potent androgens and has a germline missense-encoding polymorphism. The adrenal restrictive HSD3B1(1245A) allele limits conversion, whereas the adrenal permissive HSD3B1(1245C) allele increases DHEA metabolism to potent androgens. In the Severe Asthma Research Program (SARP) III cohort, we determined the association between DHEA-sulfate and percentage predicted forced expiratory volume in 1 s (FEV1PP). HSD3B1(1245) genotypes were assessed, and association between adrenal restrictive and adrenal permissive alleles and FEV1PP in patients with (GC) and without (noGC) daily oral glucocorticoid treatment was determined (n = 318). Validation was performed in a second cohort (SARP I&II; n = 184). DHEA-sulfate is associated with FEV1PP and is suppressed with GC treatment. GC patients homozygous for the adrenal restrictive genotype have lower FEV1PP compared with noGC patients (54.3% vs. 75.1%; P < 0.001). In patients with the homozygous adrenal permissive genotype, there was no FEV1PP difference in GC vs. noGC patients (73.4% vs. 78.9%; P = 0.39). Results were independently confirmed: FEV1PP for homozygous adrenal restrictive genotype in GC vs. noGC is 49.8 vs. 63.4 (P < 0.001), and for homozygous adrenal permissive genotype, it is 66.7 vs. 67.7 (P = 0.92). The adrenal restrictive HSD3B1(1245) genotype is associated with GC resistance. This effect appears to be driven by GC suppression of 3β-HSD1 substrate. Our results suggest opportunities for prediction of GC resistance and pharmacologic intervention.
  • Thumbnail Image
    Item
    Pancreatic β-cell dysfunction in polycystic ovary syndrome: role of hyperglycemia-induced nuclear factor-κB activation and systemic inflammation
    (American Physiological Society, 2015-05) Malin, Steven K.; Kirwan, John P.; Sia, Chang Ling; Gonzalez, Frank; Department of Obstetrics and Gynecology, IU School of Medicine
    In polycystic ovary syndrome (PCOS), oxidative stress is implicated in the development of β-cell dysfunction. However, the role of mononuclear cell (MNC)-derived inflammation in this process is unclear. We determined the relationship between β-cell function and MNC-derived nuclear factor-κB (NF-κB) activation and tumor necrosis factor-α (TNF-α) secretion in response to a 2-h 75-g oral glucose tolerance test (OGTT) in normoglycemic women with PCOS (15 lean, 15 obese) and controls (16 lean, 14 obese). First- and second-phase β-cell function was calculated as glucose-stimulated insulin secretion (insulin/glucose area under the curve for 0-30 and 60-120 min, respectively) × insulin sensitivity (Matsuda Index derived from the OGTT). Glucose-stimulated NF-κB activation and TNF-α secretion from MNC, and fasting plasma thiobarbituric acid-reactive substances (TBARS) and high-sensitivity C-reactive protein (hs-CRP) were also assessed. In obese women with PCOS, first- and second-phase β-cell function was lower compared with lean and obese controls. Compared with lean controls, women with PCOS had greater change from baseline in NF-κB activation and TNF-α secretion, and higher plasma TBARS. β-Cell function was inversely related to NF-κB activation (1st and 2nd) and TNF-α secretion (1st), and plasma TBARS and hs-CRP (1st and 2nd). First- and second-phase β-cell function also remained independently linked to NF-κB activation after adjustment for body fat percentage and TBARS. In conclusion, β-cell dysfunction in PCOS is linked to hyperglycemia-induced NF-κB activation from MNC and systemic inflammation. These data suggest that in PCOS, inflammation may play a role in impairing insulin secretion before the development of overt hyperglycemia.
  • Thumbnail Image
    Item
    Sexual Dimorphism in the Musculoskeletal System: Sex Hormones and Beyond
    (Oxford University Press, 2024-09-01) Plotkin, Lilian I.; Bruzzaniti, Angela; Pianeta, Roquelina; Anatomy, Cell Biology and Physiology, School of Medicine
    Mounting evidence indicates that whereas some fundamental aspects of bone cell differentiation and function are similar in females and males, there is a clear contribution of sex/gender on the effects of signaling molecules on bone mass and strength and, consequently, on the effects of pharmacologic approaches to treat skeletal disorders. However, until recently, most studies were designed and performed using only 1 sex, resulting in a scarcity of published information on sexual dimorphism of the musculoskeletal system, including the mandible/masticatory muscles and the axial and appendicular bones and skeletal muscles. Further, it is now recognized that scientific rigor requires the study of both males and females. Therefore, there is an increasing need to understand the molecular and cellular basis for the differential outcomes of genetic manipulations and therapeutic agent administration depending on the sex of the experimental animals. Studies have shown higher muscle mass, cancellous bone mass, and long bone width in males compared with females as well as different traits in the pelvis and the skull, which are usually used for gender identification in forensic anthropology. Yet, most reports focus on the role of sex hormones, in particular, the consequences of estrogen deficiency with menopause in humans and in ovariectomized animal models. In addition, emerging data is starting to unveil the effects of gender-affirming hormonal therapy on the musculoskeletal system. We summarize here the current knowledge on the sex/gender-dependent phenotypic characteristics of the bone and skeletal muscles in humans and rodents, highlighting studies in which side by side comparisons were made.
  • Thumbnail Image
    Item
  • Thumbnail Image
    Item
    Testosterone Usage Leading to Pulmonary Embolisms and Deep Vein Thrombosis: A Case Report and Review of the Literature
    (MDPI, 2023-04-26) Menakuru, Sasmith R.; Atta, Mona; Dhillon, Vijaypal S.; Salih, Ahmed; Medicine, School of Medicine
    Androgen usage has widely increased in recent times via prescribed and unprescribed means. Testosterone is a popular androgen taken by both athletes and the general population. While there is some evidence of androgens being thrombogenic, we report on a 19-year-old male who presented to the hospital after the usage of testosterone for one month, leading to the development of multiple pulmonary emboli and deep vein thrombosis. The authors hope to elucidate the relationship between testosterone usage and thrombosis formation.