The synthesis of glycoprotein Po and peripheral myelin protein 22 in sciatic nerve of male rats is modulated by testosterone metabolites.
Glycoprotein Po (Po) and peripheral myelin protein 22 (PMP22) are two proteins playing a crucial physiological role in the maintenance of the multilamellar structure of peripheral myelin. We here demonstrate that the removal of circulating androgens by orchidectomy induces a significant decrease of the synthesis of Po and PMP22 in the rat sciatic nerve. In case of Po, this effect may be counteracted by the subsequent treatment with testosterone metabolites, dihydrotestosterone or 5alpha-androstan-3alpha,17beta-diol (3alpha-diol). Experiments have been consequently performed in order to evaluate the role of androgen receptor (AR) in the control of Po synthesis. In vivo treatment with flutamide (i.e., an antagonist of AR) induces a decrease of the synthesis of this myelin protein in the sciatic nerve of intact male rats confirming a role for this steroid receptor. On the contrary, PMP22 seems not to be under the control of AR, but a role for GABAA receptor may be proposed. This concept is based on the findings that: (a) only 3alpha-diol, which is able to interact with GABAA receptor, is effective in stimulating the synthesis of PMP22 in the sciatic nerve of castrated male rats, and (b) flutamide treatment is ineffective in decreasing the protein levels in intact male rats. The observations here reported clearly show similarities and dissimilarities with the effects exerted by other members of neuroactive steroid family, like for instance progesterone derivatives, which will be discussed in text.
Magnaghi
Valerio
V
Department of Endocrinology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Via G. Balzaretti 9, 20133 Milan, Italy.
Ballabio
Marinella
M
Gonzalez
Lucas C
LC
Leonelli
Emanuela
E
Motta
Marcella
M
Melcangi
Roberto C
RC
D000375:Aging / Q000502:physiology; D000726:Androgen Antagonists / Q000008:administration & dosage; D000818:Animals; D005485:Flutamide / Q000008:administration & dosage; D008297:Male; D018993:Myelin P0 Protein / Q000378:metabolism*; D009185:Myelin Proteins / Q000378:metabolism*; D009919:Orchiectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D012584:Sciatic Nerve / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism*
D000726:Androgen Antagonists; D018993:Myelin P0 Protein; D009185:Myelin Proteins; C489546:Pmp22 protein, rat; D011944:Receptors, Androgen; D011963:Receptors, GABA-A; D013739:Testosterone; D005485:Flutamide