Reappearance of the thymus in old rats after orchidectomy: inhibition of regeneration by testosterone

Abstract

The thymus is a critically important organ during development, but atrophies progressively during the ageing process after puberty and is often considered to be unimportant in adult life. We have found that the thymus, which is grossly atrophied in 12- to 15-month-old male rats, is markedly restored in size 30 days after orchidectomy. The organ then appears normal histologically, having a well-defined cortex and medulla, is vascularized and filled with thymocytes. The regeneration of the thymus after orchidectomy was inhibited in a dose-related fashion by testosterone implants which produced serum concentrations of testosterone within the physiological range. The thymus was also increased in size after orchidectomy of 10-week-old rats, and testosterone inhibited the enlargement of the thymus. These results have important implications for the possible enhancement of the immune system with associated improvement of health during ageing and disease. They also point to an important physiological link between the endocrine and immune systems.

Reduced Thymic Aire Expression and Abnormal NF-κB2 Signaling in a Model of Systemic Autoimmunity

“…The thymus is sensitive to sex steroids and, postpuberty, undergoes progressive thymic atrophy, which can be reversed by castration, resulting in significant parallel expansion of both thymocytes and TEC (26,(52)(53)(54). It has been hypothesized that NZB thymic defects occur as a result of premature thymic involution (55,56).…”

Identification and Characterization of a Novel Thymus Aging Related Protein Rwdd1

“…As a consequence, it is deduced that hormones may induce, or at least influence age-associated thymic loss. Lots of evidence suggested that androgen might induce thymus involution by inhibiting thymocyte development and accelerating T cell apoptosis via AR expressed in the thymus (17)(18)(19)(20)(21)(22)(23). Furthermore, several studies suggested that AR in the thymic epithelial part might be responsible for the androgen induced thymic involution (24)(25)(26).…”

“…Red blood cells were removed using hypotonic lysis buffer (0.14 M NH 4 Cl buffered with 0.017 M Tris, pH 7.2) for 5 min at room temperature. Remaining cells were incubated with saturating amounts of phycoerythrin-conjugated antimouse CD8 antibodies and fluorescein isothiocyanateconjugated anti-mouse CD4 antibodies (BD PharMingen) and sorted with a FACSAria TM Cell Sorter (Becton Dickenson).…”

“…Much evidence suggests that androgen receptor (AR) is related to thymus involution: testosterone, ligand of AR, appeared to inhibit thymocyte development; castrated male animal showed apparent thymus enlargement, whereas testosterone treatment could restore the thymus to the original size; furthermore, androgen deprivation could lead to apparent augmentation of T cell levels and responses (4)(5)(6).…”

Influence of Castration on Development of the Thymus in Neonatal Male Rats.

“…It was recently mentioned that this involution is due to the thymocyte apoptosis induced by exposure to steroid hormones [20]. Gonadectomy, on the other hand, is known to cause thymus hypertrophy, even in aged animals [3,9]. Although these observations suggest that the testis may always exert somewhat inhibitory effect on the thymus, it is well documented that the hypothalamo-pituitary-testicular axis becomes very hypofunctional for a certain period after birth in rats [4].…”