Progesterone inhibits proliferation of human marrow colony forming cells (CFU-GM) through increased prostaglandin production by marrow macrophages.
Progesterone inhibited proliferation of granulocyte/macrophage progenitor cells (CFU-GM) in human bone marrow cultured in methylcellulose; the inhibition ranged from 8% at 3 X 10(-9) M, 22% at 3 X 10(-8) M to 38% at 3 X 10(-7) M progesterone in 14 non-malignant marrows. Depletion of marrow monocytes/macrophages with a monoclonal antibody MO2, abolished the inhibitory effect of progesterone. However, production of colony stimulating activity (CSA) did not appear to be affected, either in PHA stimulated peripheral blood or in bone marrow. Indomethacin, a prostaglandin synthetase inhibitor, greatly reduced the degree of inhibition and the addition of prostaglandin E1 (PGE1) to culture in concentrations as low as 10(-12) M completely removed any additional inhibitory effect of progesterone. PGE1 is known to inhibit only those CFU-GM bearing the Ia antigen; we observed that depletion of Ia positive CFU-GM by either 24 h incubation or by monoclonal (I2) treatment, reduced or abolished progesterone mediated inhibition. This confirms that the mechanism of progesterone inhibition of CFU-GM is mediated through increased PGE production by marrow macrophages, and subsequent inhibition by PGE of Ia positive CFU-GM.
D000527:Alprostadil / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003864:Depression, Chemical; D006098:Granulocytes / Q000187:drug effects; D006133:Growth Substances / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D009930:Organic Chemicals; D011374:Progesterone / Q000494:pharmacology*; D011458:Prostaglandins E / Q000378:metabolism*
D006133:Growth Substances; D009930:Organic Chemicals; D011458:Prostaglandins E; C042320:colony promoting activity; D011374:Progesterone; D000527:Alprostadil; D007213:Indomethacin