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.
"It remains possible that the macrophage accumulation in the functional luteal phase is a luteotrophic response to failing progesterone synthesis. Macrophage-derived products have been shown to enhance progesterone output from luteal cells in culture (Kirsch et al., 1983; Halme et al., 1985), and macrophages may secrete factors important for angiogenesis and tissue reorganization. Brännström and Norman (1993) postulated a luteotrophic effect of macrophages in the early luteal phase. "
[Show abstract][Hide abstract] ABSTRACT: It has been shown that immune cells, particularly macrophages, accumulate in the corpus luteum during luteolysis. This study aimed to investigate the effect of maternal recognition of pregnancy on the localization and numbers of macrophages in the human corpus luteum. Corpora lutea (n = 12) were obtained from normally cycling women at the time of hysterectomy and were dated on the basis of serial urinary luteinizing hormone (LH) estimation. In addition, corpora lutea (n = 4) were collected from women who had received daily doubling doses of human chorionic gonadotrophin (HCG) to mimic the hormonal changes of early pregnancy. Macrophages were localized by immunohistochemistry using an anti-CD68 antibody. Steroidogenic cells, steroidogenic cells of thecal origin and endothelial cells were identified on serial sections by immunohistochemistry for 3beta-hydroxysteroid dehydrogenase, 17alpha-hydroxylase and von Willebrand factor, respectively. The luteal cells capable of responding directly to HCG were identified by isotopic in-situ hybridization for messenger RNA encoding LH/HCG receptors. Macrophages were localized primarily to the vascular connective tissue and theca-lutein areas of the corpus luteum, although some were found in the granulosa-lutein cell layer. Macrophage numbers increased throughout the luteal phase to a maximum in the late-luteal phase (P < 0.05). Luteal 'rescue' with HCG was associated with a marked reduction in the numbers of tissue macrophages when compared with those of the late-luteal phase (P < 0.001). One of the effects of HCG during maternal recognition of pregnancy is to prevent the normal influx of macrophages into the corpus luteum. As LH/HCG receptors localized to the steroidogenic cells, this implies a fundamental role for steroidogenic cell products in the control of macrophage influx into the human corpus luteum.
Human Reproduction 09/1998; 13(9):2435-42. DOI:10.1093/humrep/13.9.2435 · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Macrophages and Leydig cells in the testes of adult rats which had been made bilaterally or unilaterally cryptorchid at birth were examined by morphometry for total mass, total number, volume density, and individual cell profile area. The total Leydig cell mass and the average size of Leydig cells, as well as the total mass and the average size of macrophages, were reduced in unilateral abdominal testes, but were unchanged in bilateral abdominal testes when compared to scrotal testes. Leydig cell and macrophage morphology were correlated suggesting a functional coupling between these cell types. The physiological significance of this cell interaction remains to be discovered.
International Journal of Andrology 03/1985; 8(1):86-96. DOI:10.1111/j.1365-2605.1985.tb00821.x · 3.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In many aspects of pro-ACTH/endorphin processing, newborn melanocytes are mature by birth. The newborn melanocytes correctly process precursor to many of the expected products including alpha MSH and beta-endorphin, the melanocytes perform tissue-specific modifications such as alpha-N-acetylation and additional proteolytic steps and they respond to dopaminergic agents but not to physiological levels of CRF or glucocorticoids. These features are retained in serum-free cultures of newborn intermediate pituitary cells. Thus, the major developmental alterations in the intermediate pituitary melanotropes involve the net 150-fold rise in pro-ACTH/endorphin synthetic rate, from birth to adulthood. In contrast, processing of pro-ACTH/endorphin in the newborn anterior lobe is not mature by birth. Both in vivo and in vitro newborn anterior pituitary corticotropes contain a large pool of pro-ACTH/endorphin, and a substantial amount of ACTH(1-39) is cleaved to ACTH(1-13)NH2 and CLIP. Surprisingly, the amount of ACTH(1-13)NH2 and beta-endorphin rises with increasing time in culture, but alpha-N-acetylation of ACTH(1-13)NH2 or beta-endorphin is not seen in the corticotropes. As in the adult, the synthesis of pro-ACTH/endorphin in newborn corticotropes is subject to regulation by CRF and glucocorticoids. In addition, glucocorticoid treatment of newborn corticotropes acts to suppress the cleavage of ACTH(1-39) to ACTH(1-13)NH2 and of beta-LPH to beta-endorphin, rendering the treated corticotropes more like the adult corticotropes. This plasticity in processing observed in the newborn corticotropes is not seen in the adult. It will be important to examine whether peptide processing patterns which are changed during this period of plasticity are permanently altered, and then what the consequences of those altered processing patterns might be.
Annals of the New York Academy of Sciences 02/1987; 512:286-99. DOI:10.1111/j.1749-6632.1987.tb24967.x · 4.38 Impact Factor
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