Macrophages: A Source of Luteotropic Cybernins

Abstract

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.

Immunohistochemical Localization of the Interleukin-1 System in the Mouse Ovary during Follicular Growth, Ovulation, and Luteinization1

“…These results are in agreement with previous studies demonstrating the presence of macrophages in the mouse ovary [18], rat ovary [31], and human ovary [32]. Our morphological observations of an intimate relationship of macrophages to luteal cells support the demonstrated capability of macrophages to stimulate progesterone production in the murine corpus luteum [33,34] and human granulosa-luteal cells [35]. Together, this evidence invokes a cooperative role of monocyte-macrophages in luteal tissue function.…”

Distribution of F4/80-Positive Cells in Developing Ovaries in the Mouse.

“…These observations lead to the speculation that the ovarian macrophages contribute to the luteolysis and atresia of follicles through their phagocytic activity. Alternatively, it has been demonstrated in the rat that the co-cultivation of ovarian macrophages with luteal cells leads to enhanced progesterone secretion from the luteal cells in vitro, indicating a paracrine function of ovarian macrophages (KIRSCH et al, 1983). It is also well known that luteal cells undergo hypertrophy with the augmented secretion of progesterone during pregnancy, However, we demonstrated that the macrophages in the corpora lutea were few in number and their cell size diminished during pregnancy.…”

Immunoreactive (ir)-Transforming Growth Factor (TGF)-.BETA. in Rat Corpus Luteum: ir-TGF.BETA. Is Expressed by Luteal Macrophages.

“…It is known that macrophages migrate into the ruptured follicle after ovulation and reside in newly formed luteal tissue [27,49]. It is inferred that these macrophages play a role in regulating luteal function by secreting cytokines [28,30,35,36,[50][51][52][53][54][55][56]. We found that the effect of PRL on progestin synthesis by rat luteal tissue was profoundly altered by removal of the spleen, a major source of peripheral macrophages [52], but, the effects of the splenectomy were virtually nullified by implanting splenocytes or splenic macrophages [51][52][53][54].…”

“…In fact, it is reported that large luteal cells and small luteal cells in rat corpus luteum were stained with the anti-TGF/31 and anti-TGF/32, respectively [24]. TGF/3 is one of the cytokines secreted from macrophages [2,33], and macrophages are known to be present in corpora lutea [25][26][27][28][29][30][31][32]. The luteal macrophage is therefore also a possible candidate for the anti-TGF/3 positive cell in the corpus luteum.…”