Effects of sex steroids on thymic epithelium and thymocyte development. 2022

Matthew D Taves, and Jonathan D Ashwell
Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.

Sex steroid hormones have major effects on the thymus. Age-related increases in androgens and estrogens and pregnancy-induced increases in progestins all cause dramatic thymic atrophy. Atrophy can also be induced by treatment with exogenous sex steroids and reversed by ablation of endogenous sex steroids. Although these observations are frequently touted as evidence of steroid lymphotoxicity, they are often driven by steroid signaling in thymic epithelial cells (TEC), which are highly steroid responsive. Here, we outline the effects of sex steroids on the thymus and T cell development. We focus on studies that have examined steroid signaling in vivo, aiming to emphasize the actions of endogenous steroids which, via TEC, have remarkable programming effects on the TCR repertoire. Due to the dramatic effects of steroids on TEC, especially thymic involution, the direct effects of sex steroid signaling in thymocytes are less well understood. We outline studies that could be important in addressing these possibilities, and highlight suggestive findings of sex steroid generation within the thymus itself.

UI MeSH Term Description Entries
D011372 Progestins Compounds that interact with PROGESTERONE RECEPTORS in target tissues to bring about the effects similar to those of PROGESTERONE. Primary actions of progestins, including natural and synthetic steroids, are on the UTERUS and the MAMMARY GLAND in preparation for and in maintenance of PREGNANCY. Gestagenic Agent,Progestagen,Progestagenic Agent,Progestational Agent,Progestational Compound,Progestational Hormone,Progestogen,Progestogens,Gestagen,Gestagen Effect,Gestagen Effects,Gestagenic Agents,Gestagenic Effect,Gestagenic Effects,Gestagens,Progestagenic Agents,Progestagens,Progestational Agents,Progestational Compounds,Progestational Hormones,Progestin,Progestin Effect,Progestin Effects,Progestogen Effect,Progestogen Effects,Agent, Gestagenic,Agent, Progestagenic,Agent, Progestational,Compound, Progestational,Effect, Gestagen,Effect, Gestagenic,Effect, Progestin,Effect, Progestogen,Effects, Gestagen,Effects, Gestagenic,Effects, Progestin,Effects, Progestogen,Hormone, Progestational
D011948 Receptors, Antigen, T-Cell Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (CD3 COMPLEX). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains. Antigen Receptors, T-Cell,T-Cell Receptors,Receptors, T-Cell Antigen,T-Cell Antigen Receptor,T-Cell Receptor,Antigen Receptor, T-Cell,Antigen Receptors, T Cell,Receptor, T-Cell,Receptor, T-Cell Antigen,Receptors, T Cell Antigen,Receptors, T-Cell,T Cell Antigen Receptor,T Cell Receptor,T Cell Receptors,T-Cell Antigen Receptors
D004848 Epithelium The layers of EPITHELIAL CELLS which cover the inner and outer surfaces of the cutaneous, mucus, and serous tissues and glands of the body. Mesothelium,Epithelial Tissue,Mesothelial Tissue,Epithelial Tissues,Mesothelial Tissues,Tissue, Epithelial,Tissue, Mesothelial,Tissues, Epithelial,Tissues, Mesothelial
D004967 Estrogens Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Estrogen,Estrogen Effect,Estrogen Effects,Estrogen Receptor Agonists,Estrogenic Agents,Estrogenic Compounds,Estrogenic Effect,Estrogenic Effects,Agents, Estrogenic,Agonists, Estrogen Receptor,Compounds, Estrogenic,Effects, Estrogen,Effects, Estrogenic,Receptor Agonists, Estrogen
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000728 Androgens Compounds that interact with ANDROGEN RECEPTORS in target tissues to bring about the effects similar to those of TESTOSTERONE. Depending on the target tissues, androgenic effects can be on SEX DIFFERENTIATION; male reproductive organs, SPERMATOGENESIS; secondary male SEX CHARACTERISTICS; LIBIDO; development of muscle mass, strength, and power. Androgen,Androgen Receptor Agonist,Androgen Effect,Androgen Effects,Androgen Receptor Agonists,Androgenic Agents,Androgenic Compounds,Agents, Androgenic,Agonist, Androgen Receptor,Agonists, Androgen Receptor,Compounds, Androgenic,Effect, Androgen,Effects, Androgen,Receptor Agonist, Androgen,Receptor Agonists, Androgen
D001284 Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Atrophies
D012739 Gonadal Steroid Hormones Steroid hormones produced by the GONADS. They stimulate reproductive organs, germ cell maturation, and the secondary sex characteristics in the males and the females. The major sex steroid hormones include ESTRADIOL; PROGESTERONE; and TESTOSTERONE. Gonadal Steroid Hormone,Sex Hormone,Sex Steroid Hormone,Sex Steroid Hormones,Sex Hormones,Hormone, Gonadal Steroid,Hormone, Sex,Hormone, Sex Steroid,Hormones, Gonadal Steroid,Hormones, Sex Steroid,Steroid Hormone, Gonadal,Steroid Hormone, Sex,Steroid Hormones, Gonadal,Steroid Hormones, Sex
D060168 Thymocytes HEMATOPOIETIC PROGENITOR CELLS that have migrated to the THYMUS where they differentiate into T-LYMPHOCYTES. Thymocytes are classified into maturational stages based on the expression of CELL SURFACE ANTIGENS. Thymocyte

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