title: Targeting muscle signaling pathways to minimize adverse effects of androgen deprivation.
abstract: Androgen deprivation therapy (ADT) is a highly effective treatment used in ∼30% of men with prostate cancer. Adverse effects of ADT on muscle are significant with consistent losses in muscle mass. However, effects of ADT on muscle strength and physical function, of most relevance to the patient, are less well understood. This is in part due to the fact that muscle effects of ADT at the cellular, genetic and protein level, critical to the understanding of the pathophysiology of sarcopenia, have come into focus only recently. This review highlights the complexity of androgen-dependent signaling in muscle with an emphasis on recent findings in the regulation of muscle growth and muscle atrophy pathways. Furthermore, the effects of ADT and testosterone on skeletal muscle histology, gene expression and protein transcription are discussed. A better mechanistic understanding of the regulation of muscle mass and function by androgens should not only pave the way for developing targeted promyogenic interventions for men with prostate cancer receiving ADT but also may have wider implications for age-associated sarcopenia in the general population.
authors.affiliation: Department of MedicineUniversity of Melbourne, Heidelberg, Victoria, AustraliaDepartment of EndocrinologyAustin Health, Studley Road Heidelberg, Victoria, 3084, Australia.
authors.forename: Casey
authors.initials: C
authors.lastname: de Rooy
authors.affiliation: Department of MedicineUniversity of Melbourne, Heidelberg, Victoria, AustraliaDepartment of EndocrinologyAustin Health, Studley Road Heidelberg, Victoria, 3084, Australia Department of MedicineUniversity of Melbourne, Heidelberg, Victoria, AustraliaDepartment of EndocrinologyAustin Health, Studley Road Heidelberg, Victoria, 3084, Australia.
authors.forename: Mathis
authors.initials: M
authors.lastname: Grossmann
authors.affiliation: Department of MedicineUniversity of Melbourne, Heidelberg, Victoria, AustraliaDepartment of EndocrinologyAustin Health, Studley Road Heidelberg, Victoria, 3084, Australia Department of MedicineUniversity of Melbourne, Heidelberg, Victoria, AustraliaDepartment of EndocrinologyAustin Health, Studley Road Heidelberg, Victoria, 3084, Australia.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Zajac
authors.affiliation: Department of MedicineUniversity of Melbourne, Heidelberg, Victoria, AustraliaDepartment of EndocrinologyAustin Health, Studley Road Heidelberg, Victoria, 3084, Australia Department of MedicineUniversity of Melbourne, Heidelberg, Victoria, AustraliaDepartment of EndocrinologyAustin Health, Studley Road Heidelberg, Victoria, 3084, Australia adac@unimelb.edu.au.
authors.forename: Ada S
authors.initials: AS
authors.lastname: Cheung
mesh_terms: D000726:Androgen Antagonists / Q000009:adverse effects*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects; D001823:Body Composition / Q000187:drug effects; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology; D009133:Muscular Atrophy / Q000139:chemically induced* / Q000517:prevention & control*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal
keywords: androgen deprivation; dynapenia; histology; sarcopenia; skeletal muscle