Neuroactive steroids and peripheral myelin proteins.
The present review summarizes observations obtained in our laboratories which underline the importance of neuroactive steroids (i.e., progesterone (PROG), dihydroprogesterone (5alpha-DH PROG), tetrahydroprogesterone (3alpha, 5alpha-TH PROG), testosterone (T), dihydrotestosterone (DHT) and 5alpha-androstan-3alpha,17beta-diol (3alpha-diol)) in the control of the gene expression of myelin proteins (i.e. glycoprotein Po (Po) and the peripheral myelin protein 22 (PMP22)) in the peripheral nervous system. Utilizing different in vivo (aged and adult male rats) and in vitro (Schwann cell cultures) experimental models, we have observed that neuroactive steroids are able to stimulate the mRNA levels of Po and PMP22. The effects of these neuroactive steroids, which are able to interact with classical (progesterone receptor, PR, and androgen receptor, AR) and non-classical (GABA(A) receptor) steroid receptors is further supported by our demonstration in sciatic nerve and/or Schwann cells of the presence of these receptors. On the basis of the observations obtained in the Schwann cells cultures, we suggest that the stimulatory effect of neuroactive steroids on Po is acting through PR, while that on PMP22 needs the GABA(A) receptor. The present findings might be of importance for the utilization of specific receptor ligands as new therapeutical approaches for the rebuilding of the peripheral myelin, particularly in those situations in which the synthesis of Po and PMP22 is altered (i.e. demyelinating diseases like Charcot-Marie-Tooth type 1A and type 1B, hereditary neuropathy with liability to pressure palsies and the Déjérine-Sottas syndrome, aging, and after peripheral injury).
Magnaghi
V
V
Department of Endocrinology and Center of Excellence for Neurodegenerative Disorders, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. magnaghi@mailserver.unimi.it
Cavarretta
I
I
Galbiati
M
M
Martini
L
L
Melcangi
R C
RC
D000375:Aging / Q000378:metabolism; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D018993:Myelin P0 Protein / Q000235:genetics / Q000378:metabolism*; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism; D013256:Steroids / Q000378:metabolism* / Q000494:pharmacology
D018993:Myelin P0 Protein; D009185:Myelin Proteins; C489546:Pmp22 protein, rat; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D011980:Receptors, Progesterone; D013256:Steroids