The action of steroid hormones on peripheral myelin proteins: a possible new tool for the rebuilding of myelin?

The present paper summarizes recent results we have obtained while studying the effect of sex steroids on the gene expression of two peripheral myelin proteins, the glycoprotein Po (Po) and the peripheral myelin protein 22 (PMP22). In particular, we have analyzed the effect of progesterone (P), testosterone (T) and their 5alpha- and 3alpha-5alpha-reduced derivatives [respectively, dihydrotestosterone (DHTT) and 5alpha-androstan-3alpha, 17beta-diol (3alpha-diol) for T, and dihydroprogesterone (DHP) and tetrahydroprogesterone (THP) for P]. The data obtained, utilizing different in vivo and in vitro experimental models, have indicated that: a) DHP is able to enhance the low messenger levels of Po present in the sciatic nerve of aged male rats; b) P, DHP and THP treatments stimulate the gene expression of Po in the sciatic nerve of adult male rats or in cultures of rat Schwann cells, while only THP is effective on PMP22; c) P and DHP are also able to increase the low messenger levels of Po present in transected sciatic nerve; d) the removal of circulating androgens by castration is able to decrease the mRNA levels of Po in the sciatic nerve, a phenomenon which is counteracted by the consequent treatment with DHT; e) the stimulatory effect of DHT on the gene expression of Po is also evident in cultures of rat Schwann cells, but in this case the effect seems to be due to the interaction of this steroid with the progesterone receptor; f) in cultures of Schwann cells PMP22 mRNA levels are stimulated only by 3alpha-diol treatment. Taken together, these observations showing the positive effects of sex steroid hormones on the gene expressions of Po and PMP22, suggest that a treatment with these molecules or their synthetic agonists may be useful in cases in which the rebuilding of myelin is necessary.