Health Communication and Health Education: Empowering Students to Educate Their Communities

Objectives: After completing this project, students will be able to: (a) use health communication research and theory to create educational materials; (b) analyze an audience and develop creative educational materials based on audience characteristics; and (c) consult with key constituents during the development of educational material

Significance of the disulphide bonds of human growth hormone

Struktura hormonu wzrostu (GH, growth hormone) stabilizowana jest dwoma wiązaniami disiarczkowymi — C53-C165 o C182-C189w ludzkim GH. Naukowcy badają rolę tych cech strukturalnych od końca lat 60. ubiegłego stulecia. Początkowe badania sugerowały, żewspomniane wiązania disiarczkowe nie są istotne dla aktywności biologicznej GH. Jednak w wyniku zastosowania bardziej zaawansowanychtechnik badawczych, a także na podstawie danych uzyskanych u pacjentów będących nosicielami mutacji genu GH1 stwierdzono,że dla aktywności biologicznej GH konieczna jest obecność wiązania disiarczkowego między cysteiną w pozycji C53 i cysteiną w pozycjiC165. Z kolei przerwanie C-końcowego wiązania disiarczkowego (C182-C189) w niewielkim zakresie wpływa na siłę działania biologicznegoGH mimo stwierdzonego w kompleksowym badaniu in vitro obniżenia powinowactwa wiązania z receptorem GH i obniżenia trwałości.W celu potwierdzenia tych wyników autorzy otrzymali myszy transgeniczne, u których zachodzi ekspresja analogu ludzkiego GH —C189A, i stwierdzili prawidłowe działanie pobudzające wzrost i prawidłowy wpływ na lipolizę. W niniejszej pracy przedstawiamy nowedane i przegląd dotychczasowych danych na temat wiązań disiarczkowych w GH. Omawiany też istotne mutacje stwierdzane u pacjentówz zaburzeniami wzrastania.Growth hormone (GH) structure is stabilised by two disulphide bonds, C53-C165 and C182-C189 in human GH. Researchers have investigatedthe role of these structural features since the late 1960s. Early studies implied that the disulphide bonds would not be importantfor biological activity of GH. However, more advanced techniques, as well as clues from patients carrying mutations in their GH1 gene,have demonstrated that the integrity of the disulphide bond between cysteines C53 and C165 is required for biological activity of GH.In contrast, disruption of the C-terminal disulphide bond (C182-C189) has only modest effects on the biological potency of GH, despitedecreased binding affinity to GH receptor and reduced stability as shown by a comprehensive in vitro study.To confirm these results, we generated transgenic mice that express a human GH analogue, C189A, and observed normal growth-promotingand lipolytic activities. In this article, we present new data and review old results concerning the disulphide bonds of GH. We also discussrelevant mutations found in patients with growth disorders

Reduced mammary gland carcinogenesis in transgenic mice expressing a growth hormone antagonist

Several reports have provided evidence that body size early in life is positively correlated with risk of subsequent breast cancer, but the biological basis for this relationship is unclear. We examined tumour incidence in transgenic mice expressing a growth hormone (GH) antagonist and in non-transgenic littermates following exposure to dimethylbenz[a]anthracene (DMBA), a well characterized murine mammary gland carcinogen. The transgenic animals had lower IGF-I levels, were smaller in terms of body size and weight, and exhibited decreased tumour incidence relative to controls. The demonstration that both body size early in life and breast cancer incidence are influenced by experimental perturbation of the GH–IGF-I axis in a transgenic model provides evidence that variability between individuals with respect to these hormones underlies the relationship between body size early in life and breast cancer risk observed in epidemiological studies. © 2001 Cancer Research Campaign http://www.bjcancer.co

Excessive growth hormone expression in male GH transgenic mice adversely alters bone architecture and mechanical strength

Patients with acromegaly have a higher prevalence of vertebral fractures despite normal bone mineral density (BMD), suggesting that GH overexpression has adverse effects on skeletal architecture and strength. We used giant bovine GH (bGH) transgenic mice to analyze the effects of high serum GH levels on BMD, architecture, and mechanical strength. Five-month-old hemizygous male bGH mice were compared with age- and sex-matched nontransgenic littermates controls (NT; n=16/group). Bone architecture and BMD were analyzed in tibia and lumbar vertebrae using microcomputed tomography. Femora were tested to failure using three-point bending and bone cellular activity determined by bone histomorphometry. bGH transgenic mice displayed significant increases in body weight and bone lengths. bGH tibia showed decreases in trabecular bone volume fraction, thickness, and number compared with NT ones, whereas trabecular pattern factor and structure model index were significantly increased, indicating deterioration in bone structure. Although cortical tissue perimeter was increased in transgenic mice, cortical thickness was reduced. bGH mice showed similar trabecular BMD but reduced trabecular thickness in lumbar vertebra relative to controls. Cortical BMD and thickness were significantly reduced in bGH lumbar vertebra. Mechanical testing of femora confirmed that bGH femora have decreased intrinsic mechanical properties compared with NT ones. Bone turnover is increased in favor of bone resorption in bGH tibia and vertebra compared with controls, and serum PTH levels is also enhanced in bGH mice. These data collectively suggest that high serum GH levels negatively affect bone architecture and quality at multiple skeletal sites

Inflammatory and Glutamatergic Homeostasis Are Involved in Successful Aging

Whole body studies using long-lived growth hormone receptor gene disrupted or knock out (GHR-KO) mice report global GH resistance, increased insulin sensitivity, reduced insulin-like growth factor 1 (IGF-1), and cognitive retention in old-age, however, little is known about the neurobiological status of these mice. The aim of this study was to determine if glutamatergic and inflammatory markers that are altered in aging and/or age-related diseases and disorders, are preserved in mice that experience increased healthspan. We examined messenger ribonucleic acid (mRNA) expression levels in the brain of 4- to 6-, 8- to 10-, and 20- to 22-month GHR-KO and normal aging control mice. In the hippocampus, glutamate transporter 1 (GLT-1) and anti-inflammatory nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB)-p50 were elevated in 8- to 10-month GHR-KO mice compared with age-matched controls. In the hypothalamus, NFκB-p50, NFκB-p65, IGF-1 receptor (IGF-1R), glutamate/aspartate transporter (GLAST), and 2-amino-3-(5-methyl-3-oxo 2,3-dihydro-1,2 oxazol-4-yl) propanoic acid receptor subunit 1 (GluA1) were elevated in 8- to 10- and/or 20- to 22-month GHR-KO mice when comparing genotypes. Finally, interleukin 1-beta (IL-1β) mRNA was reduced in 4- to 6- and/or 8- to 10-month GHR-KO mice compared with normal littermates in all brain areas examined. These data support the importance of decreased brain inflammation in early adulthood and maintained homeostasis of the glutamatergic and inflammatory systems in extended longevity

Oś hormon wzrostu–insulinopodobny czynnik wzrostu a karcynogeneza

  The growth hormone (GH) and insulin-like growth factor (IGF) system plays an important role in the regulation of cell proliferation, differentiation, apoptosis, and angiogenesis. In terms of cell cycle regulation, the GH-IGF system induces signalling pathways for cell growth that compete with other signalling systems that result in cell death; thus the final effect of these opposed forces is critical for normal and abnormal cell growth. The association of the GH-IGF system with carcinogenesis has long been hypothesised, mainly based on in vitro studies and the use of a variety of animal models of human cancer, and also on epidemiological and clinical evidence in humans. While ample experimental evidence supports a role of the GH-IGF system in tumour promotion and progression, with several of its components being currently tested as central targets for cancer therapy, the strength of evidence from patients with acromegaly, GH deficiency, or treated with GH is much weaker. In this review, we will attempt to consolidate this data. (Endokrynol Pol 2016; 67 (4): 414–426)    Oś hormon wzrostu (GH)–insulinopodobny czynnik wzrostu (IGF) odgrywa istotną rolę w regulacji proliferacji i różnicowania komórek, apoptozy i angiogenezy. Oś GH–IGF wpływa na regulację cyklu komórkowego przez pobudzenie szlaku wzrostu komórki w stosunku do szlaków sygnałowych prowadzących do śmierci komórki, a ostateczny efekt oddziaływania tych dwóch sił ma podstawowe znaczenie dla prawidłowego lub nieprawidłowego wzrostu komórki. Hipotezy na temat powiązań osi GH–IGF z karcynogenezą pojawiły się wiele lat temu, głównie w oparciu o wyniki badań in vitro oraz badań z wykorzystaniem różnych zwierzęcych modeli raka występującego u ludzi. Chociaż liczne dane doświadczalne potwierdzają rolę osi GH–IGF sprzyjającą rozwojowi i progresji nowotworów, a nad kilkoma składowymi tej osi trwają obecnie badania oceniające ich przydatność jako główne cele terapii przeciwnowotworowej, to jednak siła dowodów uzyskanych u chorych z akromegalią, niedoborem GH lub osób leczonych GH jest znacznie słabsza. W niniejszej pracy przeglądowej spróbowano zebrać wszystkie te dane. (Endokrynol Pol 2016; 67 (4): 414–426)

Odkrycie i zastosowanie pegwisomantu: antagonisty hormonu wzrostu

Growth hormone (GH) is a well established participant in several complex physiological processes including growth, differentiation, and metabolism. Recombinant human GH is a drug that has been approved for use for several clinical conditions where the action of GH is diminished or completely lacking. Thus there is considerable interest in developing novel drugs that modify the function of GH. Only in the last several decades have the detailed structural features of GH along with its interaction with its receptor been elucidated. In this review we summarise the basic structural and functional properties of GH, its receptor and their interaction. In addition, we discuss the discovery and development of an effective GH receptor antagonist, pegvisomant, and summarise potential therapeutic uses of this drug. (Pol J Endocrinol 2007; 58 (4): 322-329)Hormon wzrostu (GH, growth hormone) uczestniczy w wielu fizjologicznych procesach dotyczących wzrastania, różnicowania i metabolizmu. Leczenie rekombinowanym ludzkim GH jest akceptowane w wielu schorzeniach wiążących się z całkowitym brakiem lub zmniejszeniem działania GH. Wynika stąd znaczne zainteresowanie rozwojem nowych leków mogących modyfikować czynność GH. Dopiero niedawno wyjaśniono dokładną strukturę GH i jego interakcje z receptorem. W niniejszej pracy autorzy podsumowują wiedzę dotyczącą podstawowej budowy GH, jego receptora i interakcji między nimi. Ponadto, omówiono odkrycie i rozwój skutecznego antagonisty receptora GH, pegvisomantu i przedstawiono potencjalne możliwości zastosowania terapeutycznego tego leku

Relative Contributions of Myostatin and the GH/IGF-1 Axis in Body Composition and Muscle Strength

Myostatin, a negative regulator of muscle growth, is considered a potential therapeutic agent for individuals suffering from various muscle wasting and strength declining diseases because inhibiting Mstn signaling leads to muscular hypertrophy. In this study we investigate the interaction between myostatin and the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis in muscle function and strength. To this end, we measured hind limb grip strength and myostatin levels in two mouse models of GH gene manipulation; GH receptor knockout (GHR-/-) mice which have reduced GH/IGF-1 action, and bovine GH transgenic (bGH) mice which have excess GH/IGF-1 action. We found that specific muscle force was significantly reduced in bGH mice, and significantly increased in GHR-/- mice, compared to their respective littermate wild type controls. The expression of the mature form of myostatin was significantly increased in bGH mice, and unchanged in GHR-/- mice. In the bGH mice, the high levels of mature myostatin were accompanied by increase body weight and lean mass, consistent with other published results indicating that the IGF-1 signaling pathway is dominant over that of Mstn. Our results also suggest that in these mouse models there is an inverse relationship between muscle strength and levels of myostatin and GH, since constitutive overexpression of GH resulted in elevated levels of mature myostatin in muscle, accompanied by a reduction in strength. By contrast, in the GHR-/- mice with reduced levels of IGF-1, mature myostatin levels were unchanged and muscle strength was increased

Structure and function of a dual antagonist of the human growth hormone and prolactin receptors with site-specific PEG conjugates

Human growth hormone (hGH) is a pituitary-derived endocrine protein that regulates several critical postnatal physiologic processes including growth, organ development, and metabolism. Following adulthood, GH is also a regulator of multiple pathologies like fibrosis, cancer, and diabetes. Therefore, there is a significant pharmaceutical interest in developing antagonists of hGH action. Currently, there is a single FDA-approved antagonist of the hGH receptor (hGHR) prescribed for treating patients with acromegaly and discovered in our laboratory almost 3 decades ago. Here, we present the first data on the structure and function of a new set of protein antagonists with the full range of hGH actions—dual antagonists of hGH binding to the GHR as well as that of hGH binding to the prolactin receptor. We describe the site-specific PEG conjugation, purification, and subsequent characterization using MALDI-TOF, size-exclusion chromatography, thermostability, and biochemical activity in terms of ELISA-based binding affinities with GHR and prolactin receptor. Moreover, these novel hGHR antagonists display distinct antagonism of GH-induced GHR intracellular signaling in vitro and marked reduction in hepatic insulin-like growth factor 1 output in vivo. Lastly, we observed potent anticancer biological efficacies of these novel hGHR antagonists against human cancer cell lines. In conclusion, we propose that these new GHR antagonists have potential for development towards multiple clinical applications related to GH-associated pathologies.</p

Enhanced Cognition and Hypoglutamatergic Signaling in a Growth Hormone Receptor Knockout Mouse Model of Successful Aging.

Growth hormone receptor knockout (GHR-KO) mice are long lived with improved health span, making this an excellent model system for understanding biochemical mechanisms important to cognitive reserve. The purpose of the present study was to elucidate differences in cognition and glutamatergic dynamics between aged (20- to 24-month-old) GHR-KO and littermate controls. Glutamate plays a critical role in hippocampal learning and memory and is implicated in several neurodegenerative disorders, including Alzheimer\u27s disease. Spatial learning and memory were assessed using the Morris water maze (MWM), whereas independent dentate gyrus (DG), CA3, and CA1 basal glutamate, release, and uptake measurements were conducted in isoflurane anesthetized mice utilizing an enzyme-based microelectrode array (MEA) coupled with constant potential amperometry. These MEAs have high temporal and low spatial resolution while causing minimal damage to the surrounding parenchyma. Littermate controls performed worse on the memory portion of the MWM behavioral task and had elevated DG, CA3, and CA1 basal glutamate and stimulus-evoked release compared with age-matched GHR-KO mice. CA3 basal glutamate negatively correlated with MWM performance. These results support glutamatergic regulation in learning and memory and may have implications for therapeutic targets to delay the onset of, or reduce cognitive decline, in Alzheimer\u27s disease