Progesterone-induced smooth muscle—like cells in the subperitoneal nodules produced by estrogen: Experimental approach to leiomyomatosis peritonealis disseminata

Abstract In order to examine the pathogenesis and histogenesis of leiomyomatosis peritonealis disseminata (LPD), guinea pigs were treated with various doses of estradiol benzoate (E) (40, 80, 100, and 200 μg/day, three times a week, by intramuscular injection). After treatment for 3 months, each dose of E produced lesions simulating the disseminated pattern of LPD. Ultrastructurally, the nodules were considered to be composed of cells resembling those of fibroblast. In guinea pigs, pretreatment with estradiol benzoate (100 μg/day, three times a week intramuscularly for 3 months followed by combination treatment with E and progesterone (P) (0.5 and 1.0 mg/day, once a week, intramuscularly) for 1 to 3 months produced nodules similar to those with estrogen alone. Ultrastructurally, these nodules were composed of cells resembling smooth muscle and decidual cells. According to these results, we conjectured that estrogen differentiates and proliferates cells with the features of fibroblast-like cells from the subcoelomic totipotential mesenchyme, and these cells are differentiated into smooth muscle—like cells and decidua-like cells under the influence of both estrogen and progesterone, resulting in the production of multiple subperitoneal nodules.