Endocrine Abstracts (2004) 7 S31

Effects of neuroactive steroids on myelination

RC Melcangi, M Ballabio, LC Gonzalez, C Gyenes, E Leonelli & V Magnaghi

Department of Endocrinology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Milano, Italy.

It is now well known that peripheral nervous system (PNS) is able to synthesize neurosteroids and to convert them, or hormonal steroids coming from the periphery, in neuroactive steroids. Moreover, PNS possess both classical (e.g., progesterone receptor, PR, androgen receptor, AR) and non-classical (e.g., GABAA receptor) steroid receptors and consequently may represent a target for the action of neuroactive steroids. Our data have indicated that neuroactive steroids, like for instance progesterone, dihydroprogesterone, tetrahydroprogesterone, dihydrotestosterone and 3alpha-diol, stimulate both in vivo and in vitro (Schwann cell cultures), the expression of two important proteins of the myelin of peripheral nerves, the glycoprotein Po (Po) and the peripheral myelin protein 22 (PMP22). It is important to highlight that the mechanisms by which neuroactive steroids exert their effects on the expression of Po and PMP22 involve different kind of receptors depending on the steroid and on the myelin protein considered. In particular, the expression of Po seems to be under the control of classical steroid receptor (i.e., PR and AR) while that on PMP22 needs the GABAA receptor. Po and PMP22 play an important role for the maintenance of the multilamellar structure of the myelin of PNS, consequently we have recently assessed whether neuroactive steroids may also influence the morphology of myelinated fibers in the sciatic nerve of aged male rats. We have observed that progesterone and its derivatives (i.e., dihydroprogesterone and tetrahydroprogesterone) are able to reduce aging-associated morphological abnormalities of myelin and aging-associated myelin fiber loss in the sciatic nerve. Altogether, the present observations might suggest the utilization of neuroactive steroids as new therapeutically approaches for the rebuilding of the peripheral myelin. (Financial support: QLK6-CT-2000-00179; FIRB 2001, RBAU01kje4_001; HPMF-CT-2001-01144).

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