Progestin and antiprogestin differentially regulate the expression of insulin-like growth factors (IGF-I and IGF-II) messenger ribonucleic acid in human endometrial stromal cells.
Previous studies have shown that insulin-like growth factors (IGF-I and IGF-II) stimulate mitogenic activity in human endometrial stromal cells. In the present study, we have investigated the expression of IGF-I and -II mRNA to ascertain any autocrine growth-promoting effect in this system. Northern blot analysis revealed that endometrial stromal cells express multiple sizes of IGF-I and -II transcripts. The effect of progestin and antiprogestin was studied during decidualization of endometrial stromal cells in long-term culture. Solution hybridization and a ribonuclease protection assay of control cells revealed that the level of IGF-I mRNA was low, whereas IGF-II mRNA was always abundant. Medroxyprogesterone acetate (MPA) stimulated the expression of IGF-I mRNA > 4-fold in predecidualized cells during the first 10 days of culture. IGF-I mRNA decreased to basal level in prolonged culture when cells were decidualized. In contrast, MPA suppressed the IGF-II mRNA level by 60% in predecidualized cells, but IGF-II mRNA was highly expressed after 20 days of incubation with MPA (5-fold increase from Days 5-10 to Day 20 of culture). In progestin-pretreated cells, addition of the antiprogestin RU486 for 1-4 days reduced IGF-I mRNA by 50-90%. RU486 reversed the suppressive effect of MPA and increased IGF-II mRNA. This study indicates that progestin and antiprogestin differentially regulate IGF-I and IGF-II mRNA levels in human endometrial stromal cells.
D002478:Cells, Cultured; D004717:Endometrium / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D015735:Mifepristone / Q000494:pharmacology*; D045167:Progesterone Congeners / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism
D006727:Hormone Antagonists; D045167:Progesterone Congeners; D012333:RNA, Messenger; D015735:Mifepristone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017258:Medroxyprogesterone Acetate