The concentration of prolactin (PRL) in the blood increases with aging in the rat, and pituitary prolactinomas often develop in aged female rats. We measured blood PRL levels in the course of development of hyperprolactinemia and prolactinomas in individual rats by serial sampling of the blood of living rats. The pituitaries were examined upon the death of the rats to detect prolactinomas by immunocytochemical staining. Hyperprolactinemia in rats without pituitary tumors was inevitably followed by the development of a prolactinoma within 3 months. Rats which had no tumors at the time of death had low PRL levels throughout their lifespan. Counting of anterior pituitary cells after immunocytochemical staining for electron microscopy indicated that the number of mammotrophs increased and that the number of somatotrophs decreased in rats with hyperprolactinemia. Based on these results, we conclude that age-related hyperprolactinemia in female rats represents a precancerous state for prolactinoma.
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