Intrinsic and Extrinsic Thymic Adrenergic Networks: Sex Steroid-Dependent Plasticity

Abstract

The thymus is sexually differentiated organ providing microenvironment for T-cell precursor differentiation/maturation in the major histocompatibility complex-restricted self-tolerant T cells. With increasing age, the thymus undergoes involution leading to the decline in efficacy of thymopoiesis. Noradrenaline from thymic nerve fibers and “(nor)adrenergic” cells is involved in the regulation of thymopoiesis. In rodents, noradrenaline concentration in thymus and adrenoceptor (AR) expression on thymic cells depend on sex and age. These differences are suggested to be implicated in the development of sexual diergism and the age-related decline in thymopoiesis. The programming of both thymic sexual differentiation and its involution occurs during the critical early perinatal period and may be reprogrammed during peripubertal development. The thymic (re)programming is critically dependent on circulating levels of gonadal steroids. Although the underlying molecular mechanisms have not yet been elucidated fully, it is assumed that the gonadal steroid action during the critical perinatal/peripubertal developmental periods leads to long-lasting changes in the efficacy of thymopoiesis partly through (re)programming of “(nor)adrenergic” cell networks and AR expression on thymic cells.

Large scale meta-analysis of preclinical toxicity data for target characterisation and hypotheses generation

“…Androgen receptors are found in the thymic epithelium and are postulated to modulate thymus size and thymocyte development and accelerate thymocyte apoptosis [32,33]. B2 adrenergic receptors have been identified in the medulla of the rat thymus gland with experiments suggesting their relation with thymocyte proliferative response, histological changes and thymopoiesis [34][35][36]. Muscarinic receptors have also been reported in thymocytes and suggested to appear in late periods of cell maturation [37].…”

Microarchitecture of the Thymus Gland; Its Age and Disease-Associated Morphological Alterations, and Possible Means to Prolong Its Physiological Activity

“…So, in adult, only a thin remnant appeared in the anterior mediastinum or has entirely disappeared. Thymus gland size is also affected by the sex-steroid hormone and hypothalamic-pituitary-adrenal axes hormones [14]. It has been found that during the thymus involution, the CT which is present in the capsule, septa, perivascular tissue, and in the stroma of the cortex and medulla is getting enriched with the fibronectin contents.…”

“…During such diseases, the demarcation between the cortex and the medulla deteriorated and the medullar epithelial cells are also dispersed [16]. A rare autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is an inherited syndrome and is because of alterations in the specific gene [14]. Such gene permits the illustration of tissue related particular proteins present in the thymic medulla.…”

“…This illness is categorized as softness and fatigability of the muscle and is triggered by autoantibodies depending T cell counter to the neuromuscular junction. Its exact cause is unknown; however, it is assumed that changes in the thymus and the thymic epithelial cells is one of the main causes of its pathogenesis [14,15]. Sometimes, this disease is associated with thymic hyperplasia.…”

“…This delayed process improves immunity and may add in extension of the individual lifespan. Another new method which reduce the thymus atrophy and boost the thymus functioning is the sex-steroid ablation therapies [14]. Genetics has also an important role for determining the initial thymus size and rate of involution.…”