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      Growth Hormone(s), Testosterone, Insulin-Like Growth Factors, and Cortisol: Roles and Integration for Cellular Development and Growth With Exercise

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          Abstract

          Hormones are largely responsible for the integrated communication of several physiological systems responsible for modulating cellular growth and development. Although the specific hormonal influence must be considered within the context of the entire endocrine system and its relationship with other physiological systems, three key hormones are considered the “anabolic giants” in cellular growth and repair: testosterone, the growth hormone superfamily, and the insulin-like growth factor (IGF) superfamily. In addition to these anabolic hormones, glucocorticoids, mainly cortisol must also be considered because of their profound opposing influence on human skeletal muscle anabolism in many instances. This review presents emerging research on: (1) Testosterone signaling pathways, responses, and adaptations to resistance training; (2) Growth hormone: presents new complexity with exercise stress; (3) Current perspectives on IGF-I and physiological adaptations and complexity these hormones as related to training; and (4) Glucocorticoid roles in integrated communication for anabolic/catabolic signaling. Specifically, the review describes (1) Testosterone as the primary anabolic hormone, with an anabolic influence largely dictated primarily by genomic and possible non-genomic signaling, satellite cell activation, interaction with other anabolic signaling pathways, upregulation or downregulation of the androgen receptor, and potential roles in co-activators and transcriptional activity; (2) Differential influences of growth hormones depending on the “type” of the hormone being assayed and the magnitude of the physiological stress; (3) The exquisite regulation of IGF-1 by a family of binding proteins (IGFBPs 1–6), which can either stimulate or inhibit biological action depending on binding; and (4) Circadian patterning and newly discovered variants of glucocorticoid isoforms largely dictating glucocorticoid sensitivity and catabolic, muscle sparing, or pathological influence. The downstream integrated anabolic and catabolic mechanisms of these hormones not only affect the ability of skeletal muscle to generate force; they also have implications for pharmaceutical treatments, aging, and prevalent chronic conditions such as metabolic syndrome, insulin resistance, and hypertension. Thus, advances in our understanding of hormones that impact anabolic: catabolic processes have relevance for athletes and the general population, alike.

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          Most cited references218

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          Glucocorticoid-induced skeletal muscle atrophy.

          Many pathological states characterized by muscle atrophy (e.g., sepsis, cachexia, starvation, metabolic acidosis and severe insulinopenia) are associated with an increase in circulating glucocorticoids (GC) levels, suggesting that GC could trigger the muscle atrophy observed in these conditions. GC-induced muscle atrophy is characterized by fast-twitch, glycolytic muscles atrophy illustrated by decreased fiber cross-sectional area and reduced myofibrillar protein content. GC-induced muscle atrophy results from increased protein breakdown and decreased protein synthesis. Increased muscle proteolysis, in particular through the activation of the ubiquitin proteasome and the lysosomal systems, is considered to play a major role in the catabolic action of GC. The stimulation by GC of these two proteolytic systems is mediated through the increased expression of several Atrogenes ("genes involved in atrophy"), such as FOXO, Atrogin-1, and MuRF-1. The inhibitory effect of GC on muscle protein synthesis is thought to result mainly from the inhibition of the mTOR/S6 kinase 1 pathway. These changes in muscle protein turnover could be explained by changes in the muscle production of two growth factors, namely Insulin-like Growth Factor (IGF)-I, a muscle anabolic growth factor and Myostatin, a muscle catabolic growth factor. This review will discuss the recent progress made in the understanding of the mechanisms involved in GC-induced muscle atrophy and consider the implications of these advancements in the development of new therapeutic approaches for treating GC-induced myopathy. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting. Copyright © 2013 Elsevier Ltd. All rights reserved.
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            Transcription factor AP1 potentiates chromatin accessibility and glucocorticoid receptor binding.

            Ligand-dependent transcription by the nuclear receptor glucocorticoid receptor (GR) is mediated by interactions with coregulators. The role of these interactions in determining selective binding of GR to regulatory elements remains unclear. Recent findings indicate that a large fraction of genomic GR binding coincides with chromatin that is accessible prior to hormone treatment, suggesting that receptor binding is dictated by proteins that maintain chromatin in an open state. Combining DNaseI accessibility and chromatin immunoprecipitation with high-throughput sequencing, we identify the activator protein 1 (AP1) as a major partner for productive GR-chromatin interactions. AP1 is critical for GR-regulated transcription and recruitment to co-occupied regulatory elements, illustrating an extensive AP1-GR interaction network. Importantly, the maintenance of baseline chromatin accessibility facilitates GR recruitment and is dependent on AP1 binding. We propose a model in which the basal occupancy of transcription factors acts to prime chromatin and direct inducible transcription factors to select regions in the genome. Copyright © 2011 Elsevier Inc. All rights reserved.
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              Hormonal Responses and Adaptations to Resistance Exercise and Training

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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                25 February 2020
                2020
                : 11
                : 33
                Affiliations
                [1] 1Department of Human Sciences, The Ohio State University , Columbus, OH, United States
                [2] 2Department of Health and Exercise Science, The College of New Jersey , Ewing, NJ, United States
                [3] 3Biochemistry and Molecular Biology, The Pennsylvania State University , University Park, PA, United States
                [4] 4Department of Sports Medicine, School of Health and Rehabilitation Sciences, University of Pittsburgh , Pittsburgh, PA, United States
                [5] 5Quest Diagnostics , Secaucus, NJ, United States
                Author notes

                Edited by: Flavio Adsuara Cadegiani, Federal University of São Paulo, Brazil

                Reviewed by: Michaël R. Laurent, University Hospitals Leuven, Belgium; Gwen V. Childs, University of Arkansas for Medical Sciences, United States

                *Correspondence: William J. Kraemer kraemer.44@ 123456osu.edu

                This article was submitted to Translational Endocrinology, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2020.00033
                7052063
                32158429
                d56f8b23-314e-4a60-b4ea-09fac08aa3bb
                Copyright © 2020 Kraemer, Ratamess, Hymer, Nindl and Fragala.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 19 November 2019
                : 16 January 2020
                Page count
                Figures: 5, Tables: 2, Equations: 0, References: 238, Pages: 25, Words: 21051
                Categories
                Endocrinology
                Review

                Endocrinology & Diabetes
                anabolic,catabolic,protein synthesis,skeletal muscle,endocrine,glucocorticoid,androgen,signaling

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