A macrophage homogenate contained substances which stimulated primary cultures of mouse granulosa cells to secrete more progesterone. The response to the luteotropic substances was similar to that observed when intact macrophages were co-cultured with granulosa cells. The bioactive polypeptides present in cytosolic and particulate fractions of cell homogenates were non-dialyzable, heat labile and trypsin sensitive. When the surface of intact macrophages was treated with trypsin there was a loss of activity from the particulate fraction suggesting that some luteotropic proteins reside on the plasma membrane of mononuclear phagocytes. Treatment of macrophages with Con A but not the succinyl derivative of the lectin caused a release of luteotropic proteins with apparent molecular weights of 26,000 and 41,000. These findings in conjunction with our prior observation that macrophages must contact granulosa cells to stimulate progesterone secretion suggest that aggregation of mononuclear cell surface proteins may occur when the two cells interact thus resulting in the expression of luteotropic activity. Hence, it appears that macrophages which are found within corpus luteum may be a source of ovarian cybernins. This is the first description that a cell of the immune system can communicate at the molecular level with a steroid secreting cell of the ovary.
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