Posttranscriptional inhibition of mouse placental lactogen-II secretion by transforming growth factor beta 1: synergistic effects with epidermal growth factor and interleukin-6.
We studied the effect of transforming growth factor beta 1 (TGF beta 1) on mouse placental lactogen (mPL)-I and mPL-II secretion by primary cultures of placental cells from Days 7, 9, and 12 of pregnancy. We also studied the effects of co-incubation of epidermal growth factor (EGF) or interleukin-6 (IL-6) with TGF beta 1 on mPL-I and mPL-II secretion. TGF beta 1 at 10 ng/ml did not affect mPL-I secretion by cells from Days 7 or 9 of pregnancy or mPL-II secretion by cells from Day 7 of pregnancy but significantly inhibited mPL-II secretion by cells from Days 9 or 12 of pregnancy. The lowest concentration of TGF beta 1 that significantly inhibited mPL-II secretion by cells from Days 9 or 12 of pregnancy was 1 ng/ml. Immunocytochemistry for mPL-II indicated that treatment of placental cells from Day 12 of pregnancy with 10 ng/ml TGF beta 1 significantly reduced the number of mPL-II-containing cells. Inhibition of mPL-II secretion by TGF beta 1 was eliminated completely by addition of an anti-TGF beta 1 antibody. Northern analysis showed that steady state levels of mPL-II mRNA were not reduced by incubation of placental cells from Day 12 of pregnancy with 10 ng/ml TGF beta 1 for 5 days. EGF at 10 ng/ml significantly inhibited mPL-II secretion by cells from Day 7 of pregnancy, and addition of 10 ng/ml TGF beta 1, which did not itself inhibit mPL-II secretion by those cells, enhanced the inhibition by EGF of mPL-II secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D015850:Interleukin-6 / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D010928:Placental Lactogen / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D015850:Interleukin-6; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C062303:placental lactogen II; C085699:placental lactogen I, rat; D004815:Epidermal Growth Factor; D010928:Placental Lactogen