The effect of hypophysectomy on thymic aging in mice

Surgical removal of the pituitary (hypophysectomy) followed by endocrine supplementation in middle-aged rats has been reported to reverse immunologic decline with age. We attempted to confirm and extend these reports by using a well-defined and readily available mouse model system. Hypophysectomy and endocrine supplementation in 8- to 9-mo-old C57BL/6J (B6) male retired breeder mice improved some, but not all, T dependent immune functions tested at 15 mo of age. In hypoxed mice, spleen cell proliferation in response to phytohemagglutinin (PHA) in vitro, and delayed type hypersensitivity (DTH) responses to sheep red blood cells (SRBC) measured by footpad swelling improved to levels shown by young controls. Direct anti-SRBC plaque-forming cell (PFC) responses by spleen cells, and serum agglutination responses against SRBC were not improved. Hypoxed mice had larger thymuses and much higher ratios of cortex-medulla areas than did age-matched controls. Hair regrowth after shaving was much faster in hypoxed mice. Nevertheless, hypophysectomy reduced mean and maximum longevities. These results conflict in several ways with the previously reported studies in rats, in which direct PFC responses and maximum longevities were improved by this treatment. There have been no previous studies of the effect of hypophysectomy and endocrine supplementation on thymic aging in mice, nor has it previously been reported that this treatment causes improvements in PHA and DTH responses and in thymic morphology. These effects show that at least some aging processes are reversible in aging individuals. They also suggest that hypophysectomy of middle-aged mice will be useful for studying neuroendocrine and thymic interactions that occur during the aging process.