Oestrogen retards the development of spontaneous thymomas in BUF/Mna rats

Abstract

BUF/Mna rats develop spontaneous thymomas with nearly 100% incidence in both sexes. While the thymomas in males develop from around 9 months of age, those in females start from 13-15 months of age. To clarify the mechanism of the delay of thymomagenesis in females, the effect of sex hormones on the development of thymomas was examined after either gonadectomy or oestrogen treatment. Prepubertal ovariectomy accelerated the thymoma development in females, whereas orchiectomy did not affect it. An intraperitoneal injection of oestriol (20 mg) into males at 2 months of age remarkably diminished the thymic weight to about one-tenth of age-matched controls at 16 months of age. These results suggest that oestrogen can actually retard the onset of thymoma in spite of genetic control of its incidence. However, oestrogen did not cause thymic involution when it was injected into rats over 9 months of age. Immunohistochemically, there seemed to be no distinct difference in distribution of oestrogen-receptor-bearing epithelial cells between thymomas and 2- to 3-month-old thymuses. The oestrogen sensitivity of the thymus might be destined to be lost, as the thymic epithelial cells start neoplastic changes with the impairment of oestrogen-receptor function.

Age changes of neuromuscular junctions in the extensor digitorum longus muscle of spontaneous thymoma BUF/Mna rats

“…However, there is a discrepancy in the time of occurrence between the fine structural changes of NMJs and the anti-ryanodine receptor autoantibodies which are detected at as early as 3 months of age [15]. Furthermore, the occurrence of the autoantibodies does not appear to correlate directly with the thymoma development, since thymomas in male BUF/Mna rats start to develop at about 9 months of age [10]. Since the muscle atrophy develops slowly [1], it may take such a long period until the fine structural changes of SNAs become evident.…”

“…BUF/Mna rats spontaneously develop thymomas in an autosomal dominant manner [27] and exhibit an exacerbated muscle fatigability and weakness during aging [25,26]. The thymomas, histologically resembling human thymomas, start to develop from about 9 months after birth in males, and the incidence is 100% after 18 months of age [10]. Based on electrophysiological studies, Kato and Watanabe suggested that the motor dysfunction resulted mainly from some postsynaptic change at the site of neuromuscular junctions (NMJs) of fast twitch-type muscles [16,17].…”

Thymic malignancy in a breast cancer patient Is there an association with anti-estrogenic effects of tamoxifen?

“…In our case, the association between thymoma and breast cancer can be fully or partly explained by a common etiology such as genetic predisposition and hormonal risk factors. Sex hormones strongly influence the development of thymus tumors in spontaneous thymoma BUF/ Mna rats through their receptor within the tumor cells (10,11). Thymic epithelial cells have cytoplasmic estrogen receptors and estrogen regulates a normal cellular differentiation process indirectly via its receptor in the thymus (12).…”