REGULATION OF SYNTHESIS OF THE TRANSFORMATION-INDUCED PROTEIN, LEUKOCYTE PLASTIN, BY OVARIAN-STEROID HORMONES

Previous studies indicated that, among normal cells, only those of hem opoietic lineages expressed the abundant leukocyte phosphoprotein, L-p lastin, and that activation of the L-plastin gene frequently occurred in malignant cells of solid tumors. We discovered that the gene encodi ng L-plastin contains potential estrogen and progesterone response ele ments upstream from its promoter, suggesting that L-plastin expression is subject to ovarian steroid regulation. To determine if L-plastin s ynthesis is regulated by ovarian steroids (estrogens and progestins), we examined cultured uterine endometrial stromal cells (SC) which are known to he responsive to ovarian steroids in a fashion that approxima tes the normal endometrium. Primary SC, which synthesized estrogen rec eptor and progesterone receptor mRNA transcripts, dramatically elevate d L-plastin transcript synthesis in response to treatment with estradi ol (E2) and medroxyprogesterone acetate (MPA). Stimulation of L-plasti n synthesis by E2 and MPA was also evident by examination of protein s ynthesis using high resolution two-dimensional gel electrophoresis and Western blotting. By contrast, SC that were propagated through multip le culture passages exhibited a coordinate decline in L-plastin, estro gen receptor, and progesterone receptor transcript levels and L-plasti n protein synthesis. No other intracellular proteins could be found th at were modulated significantly by E2 and MPA, but secretory protein s ynthesis was profoundly affected by E2 and MPA. Like L-plastin synthes is, hormone-mediated secretory protein synthesis was lost after propag ation of the SC culture and reduction of estrogen receptor and progest erone receptor transcript synthesis. Our findings suggest that L-plast in synthesis is regulated coordinately with secretory protein synthesi s in endometrial SC by estrogens and progestins.