Abstract
Abstract : The pineal gland, via its hormone melatonin, inhibits the proliferation of both human and animal models of breast cancer. As humans age there is the onset of disrupted sleep leading to a significant suppression in the nocturnal levels of melatonin after age 60. We have hypothesized that the decline in pineal melatonin production, with the onset of old age, is a key factor in the age-related increase in breast cancer. Using the Buffalo rat model, we have begun to characterize the melatonin rhythm in young, middle aged and old female rats. Our studies demonstrate that the nocturnal rise in both serum and pineal melatonin is significantly blunted in old rats compared to middle aged and young rats, and is blunted in middle aged rats compared to young rats. As well, uterine MT1 melatonin receptor levels are greatly diminished in old female rats (by 80%) compared to young female rats. Finally, in our studies tissue-isolated% transplanted mammary tumors grew significantly faster and were less melatonin-responsive in old rats as compared to middle and young aged rats. In addition, tumors grown in old rats showed decreased expression of ER alpha and MT1 melatonin receptor, but greatly enhanced expression of the growth factor TGF alpha.
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