title: Age-associated remodeling of thymopoiesis: role for gonadal hormones and catecholamines.
abstract: The present review summarizes recent data on age-related thymic changes termed thymic involution, and highlights the putative role of perturbances in extrathymical and, possibly, intrathymical production of gonadal steroids and catecholamines in this process. Thymic involution has been envisaged as an extremely complex process involving multifactorial mechanisms along the bone marrow-thymic axis that accounts for the major manifestations of immunosenescence. These mechanisms include basic cell aging processes (for example, cell replication and programmed cell death) and processes unique to the immune system (such as generation of the T cell receptor repertoire and control of potentially autoreactive cells). Given that the onset of age-associated thymic involution coincides with the rise in gonadal steroid levels at puberty, a causal link between these events has been suggested. It has been shown that: (1) peripubertal gonadectomy causes substantial decrease in the level of noradrenaline in adult male and female thymus and (2) catecholamines, acting via alpha- and beta-adrenoceptor, produce suppressive effects on the thymic cellularity and production of both effector and regulatory T cells. Furthermore, the possibility that gonadal steroids contribute to thymic involution is discussed in this paper. In light of recent data indicating that effects of gonadal hormone deprivation on the thymic cellularity and function are long lasting but transitory, a putative role for the intrathymic sex steroid/catecholamine production in assuring the organ involution, under conditions of their limited supply by extrathymic sources, is also considered.
authors.affiliation: Immunology Research Centre Branislav Janković, Institute of Immunology and Virology Torlak, Faculty of Pharmacy, Belgrade, Serbia. Gordana.Leposavic@pharmacy.bg.ac.yu
authors.forename: Gordana
authors.initials: G
authors.lastname: Leposavić
authors.forename: Milica
authors.initials: M
authors.lastname: Perisić
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology*; D000818:Animals; D001284:Atrophy; D001853:Bone Marrow / Q000276:immunology; D002395:Catecholamines / Q000502:physiology*; D016922:Cellular Senescence; D017637:Clonal Deletion / Q000502:physiology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D007121:Immunocompetence; D038041:Lymphopoiesis / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D011627:Puberty / Q000276:immunology / Q000502:physiology; D051381:Rats; D011941:Receptors, Adrenergic / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D017154:Stromal Cells / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development* / Q000473:pathology
chemical_list: D002395:Catecholamines; D012739:Gonadal Steroid Hormones; D011941:Receptors, Adrenergic; D011956:Receptors, Cell Surface