Actions of progesterone and its 5alpha-reduced metabolites on the major proteins of the myelin of the peripheral nervous system.
The sciatic nerve, and the Schwann cells in particular, are able to synthesize progesterone and possess the enzymes forming the 5alpha-reduced and the 3alpha-5alpha-reduced derivatives of progesterone: dihydroprogesterone and tetrahydroprogesterone. Moreover, the progesterone receptor (PR) is present in the sciatic nerve and in Schwann cell cultures. These facts suggest that progesterone and its derivatives might play a role in the control of the synthesis of the two major proteins of the peripheral nervous system (PNS): the glycoprotein Po (Po) and peripheral myelin protein 22 (PMP22). We have shown that: (a) dihydroprogesterone enhances the low mRNA levels of Po in the sciatic nerve of aged male rats; (b) progesterone and its derivatives stimulate the gene expression of Po in the sciatic nerve of adult rats and in Schwann cell cultures; (c) tetrahydroprogesterone increases PMP22 gene expression in the sciatic nerve of adult rats and in Schwann cell cultures. In additional experiments, utilizing agonists and antagonists of PR and GABAA receptor, we have observed that progesterone and its derivatives control Po gene expression via the PR, while tetrahydroprogesterone modulates the expression of PMP22 through the GABAA receptor.
Martini
Luciano
L
Department of Endocrinology, Center of Excellence on Neurodegenerative Diseases, University of Milan, Via G. Balzaretti 9, 20133 Milan, Italy.
Magnaghi
Valerio
V
Melcangi
Roberto C
RC
D000818:Animals; D002478:Cells, Cultured; D008297:Male; D018993:Myelin P0 Protein / Q000378:metabolism; D009185:Myelin Proteins / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D017933:Peripheral Nervous System / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011980:Receptors, Progesterone / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism; D012584:Sciatic Nerve / Q000378:metabolism
D018993:Myelin P0 Protein; D009185:Myelin Proteins; C489546:Pmp22 protein, rat; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D011374:Progesterone