Regulation of synthesis of the transformation-induced protein, leukocyte plastin, by ovarian steroid hormones.

ABSTRACT

Previous studies indicated that, among normal cells, only those of hemopoietic lineages expressed the abundant leukocyte phosphoprotein, L-plastin, and that activation of the L-plastin gene frequently occurred in malignant cells of solid tumors. We discovered that the gene encoding L-plastin contains potential estrogen and progesterone response elements upstream from its promoter, suggesting that L-plastin expression is subject to ovarian steroid regulation. To determine if L-plastin synthesis is regulated by ovarian steroids (estrogens and progestins), we examined cultured uterine endometrial stromal cells (SC) which are known to be responsive to ovarian steroids in a fashion that approximates the normal endometrium. Primary SC, which synthesized estrogen receptor and progesterone receptor mRNA transcripts, dramatically elevated L-plastin transcript synthesis in response to treatment with estradiol (E2) and medroxyprogesterone acetate (MPA). Stimulation of L-plastin synthesis by E2 and MPA was also evident by examination of protein synthesis using high-resolution two-dimensional gel electrophoresis and Western blotting. By contrast, SC that were propagated through multiple culture passages exhibited a coordinate decline in L-plastin, estrogen receptor, and progesterone receptor transcript levels and L-plastin protein synthesis. No other intracellular proteins could be found that were modulated significantly by E2 and MPA, but secretory protein synthesis was profoundly affected by E2 and MPA. Like L-plastin synthesis, hormone-mediated secretory protein synthesis was lost after propagation of the SC culture and reduction of estrogen receptor and progesterone receptor transcript synthesis. Our findings suggest that L-plastin synthesis is regulated coordinately with secretory protein synthesis in endometrial SC by estrogens and progestins.