Progesterone derivatives are able to influence peripheral myelin protein 22 and P0 gene expression: possible mechanisms of action.
The present study has analyzed the effect of progesterone and its derivatives (dihydroprogesterone and tetrahydroprogesterone) on the gene expression of the peripheral myelin protein 22 utilizing in vivo and in vitro models. The data obtained indicate that tetrahydroprogesterone is able to stimulate the gene expression of peripheral myelin protein 22 both in vivo (in adult but not in old animals) and in Schwann cell cultures. An effect of this steroid, which is known to interact with the GABA(A) receptor, would not be surprising, since in the present study we show the presence in Schwann cells and in the sciatic nerve of the messengers for several subunits (alpha2, alpha3, beta1, beta2, and beta3) of the GABA(A) receptor. An effect of tetrahydroprogesterone is also evident on the gene expression of another myelin protein, the peripheral myelin protein zero. However, in this case also dihydroprogesterone, which is able to bind the progesterone receptor, is involved, both in old and adult animals, in the stimulation of messengers levels of this myelin protein. In conclusion, the present data show that the gene expression of two important peripheral myelin proteins can be influenced by progesterone derivatives. The hypothesis has been put forward that part of their effects might occur not through the classical progesterone receptor, but rather via an interaction with the GABA(A) receptor.
Melcangi
R C
RC
Department of Endocrinology, University of Milan, Italy. melcangi@imiucca.csi.unimi.it
Magnaghi
V
V
Cavarretta
I
I
Zucchi
I
I
Bovolin
P
P
D'Urso
D
D
Martini
L
L
D004092:20-alpha-Dihydroprogesterone / Q000494:pharmacology*; D000375:Aging; D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D018993:Myelin P0 Protein / Q000235:genetics*; D009185:Myelin Proteins / Q000235:genetics*; D011280:Pregnanolone / Q000378:metabolism / Q000494:pharmacology*; D011374:Progesterone / Q000031:analogs & derivatives / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism
D018993:Myelin P0 Protein; D009185:Myelin Proteins; C489546:Pmp22 protein, rat; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D011980:Receptors, Progesterone; D004092:20-alpha-Dihydroprogesterone; D011374:Progesterone; D011280:Pregnanolone