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Neonatal testosterone imprinting affects thymus development and leads to phenotypic rejuvenation and masculinization of the peripheral blood T-cell compartment in adult female rats
Exposure of female rodents to testosterone in the critical neonatal period produces defeminization/masculinization of the hypothalamo-pituitary-gonadal (HPG) axis, i.e. neonatal androgenization and postpones axis maturation. To address the hypothesis that HPG axis signaling is involved in the programming of thymic maturation/involution and sexual differentiation we studied the impact of neonatal androgenization on thymic cellularity, development of effector and regulatory T cells, and phenotypic characteristics of peripheral blood T lymphocytes in adult rats. A single injection of testosterome on postnatal day 2 postponed thymic maturation/involution as revealed by organ hypercellularity, increased cellularity of the most mature (CD4+CD8- and CD4-CD8+) TCR alpha beta(high) thymocyte and both recent thymic emigrant (RTE) subsets and caused phenotypic efeminization/masculinization of thymic (decreased CD4+CD8-TCR alpha beta(high)/CD4-CD8+TCR alpha beta(high) cell ratio) and peripheral bl...ood T-cell compartments (decreased CD4+RTE/CD8+RTE and CD4+/CD8+ cell ratio). In addition, neonatal androgenization increased the relative and absolute numbers of both CD4+CD25+Foxp3+ and natural killer (NK) regulatory T cells in peripheral blood. These findings, in conjunction with thymocyte overexpression of Thy-1 that is assumed to reduce negative selection affecting self-reactive cell generation, suggest a new relationship between self-reactive and regulatory T cells. In conclusion, our study provides additional evidence for a role of HPG signals (i.e. sex steroids and gonadotropins) in programming the kinetics of thymic maturation/involution and in establishing immunological sexual dimorphism. (C) 2008 Elsevier Inc. All rights reserved.
TY - JOUR
AU - Leposavić, Gordana
AU - Perišić, Milica
AU - Kosec, Duško
AU - Arsenović-Ranin, Nevena
AU - Radojević, Katarina
AU - Stojić-Vukanić, Zorica
AU - Pilipović, Ivan
PY - 2009
UR - http://intor.torlakinstitut.com/handle/123456789/289
AB - Exposure of female rodents to testosterone in the critical neonatal period produces defeminization/masculinization of the hypothalamo-pituitary-gonadal (HPG) axis, i.e. neonatal androgenization and postpones axis maturation. To address the hypothesis that HPG axis signaling is involved in the programming of thymic maturation/involution and sexual differentiation we studied the impact of neonatal androgenization on thymic cellularity, development of effector and regulatory T cells, and phenotypic characteristics of peripheral blood T lymphocytes in adult rats. A single injection of testosterome on postnatal day 2 postponed thymic maturation/involution as revealed by organ hypercellularity, increased cellularity of the most mature (CD4+CD8- and CD4-CD8+) TCR alpha beta(high) thymocyte and both recent thymic emigrant (RTE) subsets and caused phenotypic efeminization/masculinization of thymic (decreased CD4+CD8-TCR alpha beta(high)/CD4-CD8+TCR alpha beta(high) cell ratio) and peripheral blood T-cell compartments (decreased CD4+RTE/CD8+RTE and CD4+/CD8+ cell ratio). In addition, neonatal androgenization increased the relative and absolute numbers of both CD4+CD25+Foxp3+ and natural killer (NK) regulatory T cells in peripheral blood. These findings, in conjunction with thymocyte overexpression of Thy-1 that is assumed to reduce negative selection affecting self-reactive cell generation, suggest a new relationship between self-reactive and regulatory T cells. In conclusion, our study provides additional evidence for a role of HPG signals (i.e. sex steroids and gonadotropins) in programming the kinetics of thymic maturation/involution and in establishing immunological sexual dimorphism. (C) 2008 Elsevier Inc. All rights reserved.
PB - Academic Press Inc Elsevier Science, San Diego
T2 - Brain Behavior and Immunity
T1 - Neonatal testosterone imprinting affects thymus development and leads to phenotypic rejuvenation and masculinization of the peripheral blood T-cell compartment in adult female rats
EP - 304
IS - 2
SP - 294
VL - 23
DO - 10.1016/j.bbi.2008.11.002
ER -
@article{
author = "Leposavić, Gordana and Perišić, Milica and Kosec, Duško and Arsenović-Ranin, Nevena and Radojević, Katarina and Stojić-Vukanić, Zorica and Pilipović, Ivan",
year = "2009",
abstract = "Exposure of female rodents to testosterone in the critical neonatal period produces defeminization/masculinization of the hypothalamo-pituitary-gonadal (HPG) axis, i.e. neonatal androgenization and postpones axis maturation. To address the hypothesis that HPG axis signaling is involved in the programming of thymic maturation/involution and sexual differentiation we studied the impact of neonatal androgenization on thymic cellularity, development of effector and regulatory T cells, and phenotypic characteristics of peripheral blood T lymphocytes in adult rats. A single injection of testosterome on postnatal day 2 postponed thymic maturation/involution as revealed by organ hypercellularity, increased cellularity of the most mature (CD4+CD8- and CD4-CD8+) TCR alpha beta(high) thymocyte and both recent thymic emigrant (RTE) subsets and caused phenotypic efeminization/masculinization of thymic (decreased CD4+CD8-TCR alpha beta(high)/CD4-CD8+TCR alpha beta(high) cell ratio) and peripheral blood T-cell compartments (decreased CD4+RTE/CD8+RTE and CD4+/CD8+ cell ratio). In addition, neonatal androgenization increased the relative and absolute numbers of both CD4+CD25+Foxp3+ and natural killer (NK) regulatory T cells in peripheral blood. These findings, in conjunction with thymocyte overexpression of Thy-1 that is assumed to reduce negative selection affecting self-reactive cell generation, suggest a new relationship between self-reactive and regulatory T cells. In conclusion, our study provides additional evidence for a role of HPG signals (i.e. sex steroids and gonadotropins) in programming the kinetics of thymic maturation/involution and in establishing immunological sexual dimorphism. (C) 2008 Elsevier Inc. All rights reserved.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Brain Behavior and Immunity",
title = "Neonatal testosterone imprinting affects thymus development and leads to phenotypic rejuvenation and masculinization of the peripheral blood T-cell compartment in adult female rats",
pages = "304-294",
number = "2",
volume = "23",
doi = "10.1016/j.bbi.2008.11.002"
}
Leposavić, G., Perišić, M., Kosec, D., Arsenović-Ranin, N., Radojević, K., Stojić-Vukanić, Z.,& Pilipović, I.. (2009). Neonatal testosterone imprinting affects thymus development and leads to phenotypic rejuvenation and masculinization of the peripheral blood T-cell compartment in adult female rats. in Brain Behavior and Immunity
Academic Press Inc Elsevier Science, San Diego., 23(2), 294-304.
https://doi.org/10.1016/j.bbi.2008.11.002
Leposavić G, Perišić M, Kosec D, Arsenović-Ranin N, Radojević K, Stojić-Vukanić Z, Pilipović I. Neonatal testosterone imprinting affects thymus development and leads to phenotypic rejuvenation and masculinization of the peripheral blood T-cell compartment in adult female rats. in Brain Behavior and Immunity. 2009;23(2):294-304.
doi:10.1016/j.bbi.2008.11.002 .
Leposavić, Gordana, Perišić, Milica, Kosec, Duško, Arsenović-Ranin, Nevena, Radojević, Katarina, Stojić-Vukanić, Zorica, Pilipović, Ivan, "Neonatal testosterone imprinting affects thymus development and leads to phenotypic rejuvenation and masculinization of the peripheral blood T-cell compartment in adult female rats" in Brain Behavior and Immunity, 23, no. 2 (2009):294-304,
https://doi.org/10.1016/j.bbi.2008.11.002 . .
