Tumours originating from the thymic epithelial cells are called thymomas. Akt signaling in thymic epithelial cells, promoting their proliferation and thus thymic size growth. Physical changes during puberty such as thymic involution also affect immunological response. It may also mediate adhesion between thymocytes and thymic stroma. T-lymphopoiesis does not occur automatically but requires signals generated from the thymic stromal cells. The "Ak" in Akt refers to the AKR mouse strain that develops spontaneous thymic lymphomas. IL-25, IL-33 and TSLP (thymic stromal lymphopoietin). There are also hypotheses that suggest that thymic involution is directly adaptive. Cellular sources for XCL1 include activated thymic and peripheral blood CD8+ T cells. Entero-pancreatic gastrinomas and thymic and bronchial carcinoids are the leading cause of morbidity and mortality. In April 1963, toxicity tests for pronethalol showed results of thymic tumours in mice. It then begins to decrease in size and activity in a process called thymic involution. Possible future therapies include senolytic drugs, probiotics, cytomegalovirus vaccine, and thymic replacement. Fat and connective tissue fills a part of the thymic volume. Proportional to thymic size, thymic activity (T cell output) is most active before puberty.