Progesterone stimulates the activity of the promoters of peripheral myelin protein-22 and protein zero genes in Schwann cells.
To understand better the mechanisms by which progesterone (PROG) promotes myelination in the PNS, cultured rat Schwann cells were transiently transfected with reporter constructs in which luciferase expression was controlled by the promoter region of either the peripheral myelin protein-22 (PMP22) or the protein zero (P0) genes. PROG stimulated the P0 promoter and promoter 1, but not promoter 2, of PMP22. The effect of PROG was specific, as estradiol and testosterone only weakly activated promoters. Dose-response curves for stimulation of both promoter constructs by PROG were biphasic. RU486, a PROG antagonist, did not abolish the effect of PROG, but stimulated promoter activities by itself. In the human carcinoma cell line T47D expressing high levels of PROG receptor, PROG did not stimulate the P0 and PMP22 promoters, whereas the promoter region of the mouse mammary tumor virus was fully activated. Thus, the activation by PROG of promoter activity of two peripheral myelin protein genes is Schwann-cell specific.
Désarnaud
F
F
INSERM U488, Le Kremlin-Bicêtre, France.
Do Thi
A N
AN
Brown
A M
AM
Lemke
G
G
Suter
U
U
Baulieu
E E
EE
Schumacher
M
M
D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018993:Myelin P0 Protein / Q000235:genetics*; D009185:Myelin Proteins / Q000235:genetics*; D011374:Progesterone / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018993:Myelin P0 Protein; D009185:Myelin Proteins; C073687:PMP22 protein, human; C489545:Pmp22 protein, mouse; C489546:Pmp22 protein, rat; D005576:Colforsin; D011374:Progesterone