Regulation of synthesis of the transformation-induced protein, leukocyte plastin, by ovarian steroid hormones.
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.
Palo Alto Medical Foundation Research Institute, California 94301.
J
J
Leavitt
Z P
ZP
Chen
C J
CJ
Lockwood
F
F
Schatz
D002478:Cells, Cultured; D004717:Endometrium / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008525:Medroxyprogesterone / Q000494:pharmacology*; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D010750:Phosphoproteins / Q000096:biosynthesis*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism*
D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C026742:plastin; D004958:Estradiol; D008525:Medroxyprogesterone