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Item Characterization of hormone-stimulated Na+ transport in a high-resistance clone of the MDCK cell line(1996-08) Blazer-Yost, Bonnie; Record, Rae D.; Oberleithner, HansThe Madin-Darby canine kidney (MDCK) cell line forms an epithelial monolayer which expresses many of the morphological and functional properties of the renal collecting duct. The C7 subclone of the parent line forms an epithelium which expresses many of the characteristics of principal cells. The MDCK-C7 subclone forms a high-resistance epithelium that is capable of vectorial ion transport. We have found that this epithelium responds to aldosterone, antidiuretic hormone (ADH) and insulin like growth factor 1 (IGF1) with increases in amiloride-sensitive Na+ transport. The responses to aldosterone and ADH follow time-courses that are consistent with the action of these hormones in vivo. This is the first demonstration of IGF1-induced Na+ reabsorption in a mammalian model system. Interestingly, a maximal response to any one of these natriferic factors does not inhibit a subsequent response to another hormone. These studies indicate that the C7 subclone retains many of the natriferic responses of the native principal cells and is an ideal model for studying hormonal modulation of Na+ transport.Item Differential effects of brefeldin A on hormonally regulated Na + transport in a model renal epithelial cell line(1994) Blazer-Yost, Bonnie; Coupaye-Gerard, Brigitte; Kim, Hyun Jin; Singh, AnupNa+ transport in renal epithelia is regulated by a wide variety of endogenous and exogenous cellular factors. Although most natriferic agents have an action on the amiloride-sensitive Na+ channel, the biochemical pathways which precede activation of the channel remain incompletely defined. One approach to dissecting such intricate pathways is to perturb a specific cellular process and determine its importance in the postulated mechanism. The current studies examine the effect of brefeldin A (BFA), an inhibitor of the central vacuolar system, on basal as well as aldosterone-, insulin-, and forskolin-stimulated Na+ transport. In the A6 cell line, BFA had a time-dependent effect on basal transport. Aldosterone-induced Na+ transport was sensitive to BFA while insulin's action was only partially blocked and forskolin-stimulated Na+ transport was relatively resistant to the action of the inhibitor. These studies highlight differences as well as points of convergence in the natriferic pathways.Item The endocrine regulation of alcohol dehydrogenase gene expression(1993) Alqulali, Mona SayedItem Expansion of specialized epidermis induced by hormonal state and mechanical strain(Elsevier, 2015-05) Wu, Hsin-Jung; Easwaran, Teresa; Offutt, Carlos D.; Elgar, Richard Levi; Spandau, Dan F.; Koyama, Sachiko; Foley, John; Department of Medicine, IU School of MedicineIn mammals, some sites of specialized skin such as the palms, soles, and lips grow proportionally with the animal. However, other types of specialized skin such as the nipple and anal/genital region are dramatically altered with changes of reproductive status. The specific cell types that mediate the growth of these sites have not been identified. In the mouse, we observed a dramatic expansion of the specialized epidermis of the nipple, coupled to changes in connective tissue and hair shaft density, which we designate as areola formation. During this process thymidine analog uptake was elevated in the epidermis and hair follicles. Although there were no changes in connective tissue cell proliferation, we did observe an altered expression of extracellular matrix genes. In addition, the fibroblasts of the virgin nipple areola and region showed increased transcript and protein levels for estrogen, progesterone, relaxin, and oxytocin relative to those of ventral skin. To determine the role of pregnancy, lactation hormonal milieu, and localized mechanical strain on areola formation, we created models that separated these stimuli and evaluated changes in gross structure, proliferation and protein expression. While modest increases of epidermal proliferation and remodeling of connective tissue occurred as a result of individual stimuli, areola formation required exposure to pregnancy hormones, as well as mechanical strain.Item Expensive Egos: Narcissistic Males Have Higher Cortisol(PLOS, 2012-01-23) Reinhard, David A.; Konrath, Sara H.; Lopez, William D.; Cameron, Heather G.Background Narcissism is characterized by grandiosity, low empathy, and entitlement. There has been limited research regarding the hormonal correlates of narcissism, despite the potential health implications. This study examined the role of participant narcissism and sex on basal cortisol concentrations in an undergraduate population. Methods and Findings Participants were 106 undergraduate students (79 females, 27 males, mean age 20.1 years) from one Midwestern and one Southwestern American university. Narcissism was assessed using the Narcissistic Personality Inventory, and basal cortisol concentrations were collected from saliva samples in a laboratory setting. Regression analyses examined the effect of narcissism and sex on cortisol (log). There were no sex differences in basal cortisol, F (1,97) = .20, p = .65, and narcissism scores, F (1,97) = .00, p = .99. Stepwise linear regression models of sex and narcissism and their interaction predicting cortisol concentrations showed no main effects when including covariates, but a significant interaction, β = .27, p = .04. Narcissism was not related to cortisol in females, but significantly predicted cortisol in males. Examining the effect of unhealthy versus healthy narcissism on cortisol found that unhealthy narcissism was marginally related to cortisol in females, β = .27, p = .06, but significantly predicted higher basal cortisol in males, β = .72, p = .01, even when controlling for potential confounds. No relationship was found between sex, narcissism, or their interaction on self-reported stress. Conclusions Our findings suggest that the HPA axis is chronically activated in males with unhealthy narcissism. This constant activation of the HPA axis may have important health implications.Item Hormonal aspects of intestinal absorption of valine(1965) Islam, SirajulItem Hormonal regulation of gene expression and cellular interactions in growth of the uterus(1996) Everett, Lynn M.Item Mapping the Nephron Exercise Incorporates Multiple Learning Strategies(Association of American Medical Colleges, 2017-09-28) Hopper, Mari K.; Anderson, Maria A.; Lipp, Sarah N.; Cellular and Integrative Physiology, School of MedicineIntroduction: Understanding the location and action of nephron transporters and channels is important to the understanding of renal function. As each region of the nephron is unique in its inclusion of specific transporters and channels, mapping of the nephron is an effective first step in understanding overall nephron processing. We describe a small-group, active-learning exercise that facilitates students' ability to understand renal processing within each region of the nephron. Methods: Following an overview lecture on renal transporters and channels, small groups of students worked cooperatively to map the nephron. This 2-hour, collaborative exercise was developed to reinforce key concepts in renal processing of ions and nutrients and, at the same time, utilize effective learning strategies. Learning strategies incorporated in this exercise include small-group collaboration, peer teaching, retrieval practice using an audience response system, and elaboration through discussion. Results: Written examination was used to assess student understanding. Students demonstrated higher performance on a subset of questions related to this learning activity compared to the overall exam. Highly positive feedback was provided by a convenience sample of students completing an anonymous survey. Discussion: This nephron-mapping exercise was an effective means to promote synthesis and analysis of lecture content and engage students in methods that enhance learning.Item Metabolic activity in the insular cortex and hypothalamus predicts hot flashes: an FDG-PET study(OUP, 2012-09) Joffe, Hadine; Deckersbach, Thilo; Lin, Nancy U.; Makris, Nikos; Skaar, Todd C.; Rauch, Scott L.; Dougherty, Darin D.; Hall, Janet E.CONTEXT: Hot flashes are a common side effect of adjuvant endocrine therapies (AET; leuprolide, tamoxifen, aromatase inhibitors) that reduce quality of life and treatment adherence in breast cancer patients. Because hot flashes affect only some women, preexisting neurobiological traits might predispose to their development. Previous studies have implicated the insula during the perception of hot flashes and the hypothalamus in thermoregulatory dysfunction. OBJECTIVE: The aim of the study was to understand whether neurobiological factors predict hot flashes. DESIGN: [18F]-Fluorodeoxyglucose (FDG) positron emission tomography (PET) brain scans coregistered with structural magnetic resonance imaging were used to determine whether metabolic activity in the insula and hypothalamic thermoregulatory and estrogen-feedback regions measured before and in response to AET predict hot flashes. Findings were correlated with CYP2D6 genotype because of CYP2D6 polymorphism associations with tamoxifen-induced hot flashes. OUTCOME MEASURES: We measured regional cerebral metabolic rate of glucose uptake (rCMRglu) in the insula and hypothalamus on FDG-PET. RESULTS: Of 18 women without hot flashes who began AET, new-onset hot flashes were reported by 10 (55.6%) and were detected objectively in nine (50%) participants. Prior to the use of all AET, rCMRglu in the insula (P ≤ 0.01) and hypothalamic thermoregulatory (P = 0.045) and estrogen-feedback (P = 0.007) regions was lower in women who reported developing hot flashes. In response to AET, rCMRglu was further reduced in the insula in women developing hot flashes (P ≤ 0.02). Insular and hypothalamic rCMRglu levels were lower in intermediate than extensive CYP2D6 metabolizers. CONCLUSIONS: Trait neurobiological characteristics predict hot flashes. Genetic variability in CYP2D6 may underlie the neurobiological predisposition to hot flashes induced by AET.