A direct effect of prolactin and placental lactogen on mammary epithelial nuclei.
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Biomedical subjects
Publications and source records attributed to Y J Topper.
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Insulin-like material can be extracted from insulin-Sepharose. This soluble material elicits super-insulin responses from mammary epithelial cells. It stimulates the accumulation of alpha-aminoisobutyric acid by virgin mouse mammary cells, which are unresponsive to insulin itself. It exerts a greater stimulatory effect on mammary cells from pregnant mice than insulin. It also is more efficacious than insulin as a stimulant of DNA synthesis and the combined activities of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and phosphogluconate dehydrogenase (EC 1.1.1.43). Its specific biological activity on these cells is more than five times greater than that of insulin.
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Prolactin administration to mature virgin mice leads to prolilferation of epithelium of the mammary gland. In organ culture, prolactin is not mitogenic, but insulin and insulin-free serum are. These observations are reconciled by the finding that insensitive epithelium is sensitized to insulin and/or serum by prolactin treatment in vivo. Thus, it appears that prolactin acts indirectly as a mitogen by rendering the cells susceptible to the aforementioned mitogens.
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In terms of the rate of accumulation of alpha-aminoisobutyric acid, mammary epithelial cells from mature virgin mice respond rapidly to insulin covalently bound to sepharose particles, but do not respond initially to soluble insulin in vitro. The response to insulin-sepharose is prevented if the cells are first exposed to insulin. These observations may provide new insight into the dynamics of insulin action.
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Explants from mammary gland of pregnant mice are sensitive to insulin, but corresponding explants from mature, virgin mice are insensitive to insulin in certain respects. Isolated virgin tissue can acquire insulin-sensitivity independent of exogenous insulin. Some endocrinological and developmental implications are discussed.
The effects of insulin, hydrocortisone, and prolactin on the morphology of explants from midpregnant mouse mammary glands were studied. Insulin promotes the formation of daughter cells within the alveolar epithelium which are ultrastructurally indistinguishable from the parent cells. The addition of hydrocortisone to the medium containing insulin brings the daughter cells to a new, intermediate level of ultrastructural development by effecting an extensive increase of the rough endoplasmic reticulum (RER) throughout the cytoplasm and an increase in the lateral paranuclear Golgi apparatus. When prolactin is added to the insulin-hydrocortisone medium, the daughter cells complete their ultrastructural differentiation. There is a translocation of the RER, Golgi apparatus, and nucleus and the appearance of secretory protein granules within the cytoplasm. There is excellent correlation between the ultrastructural appearance of the alveoli and their capacity to synthesize casein.
Hydrocortisone is necessary for the formation of rough endoplasmic reticulum in mammary alveolar epithelial cells. This membrane system is required for the synthesis of the milk protein, casein, but it is not required for the synthesis of a nonmilk protein fraction.