PMID- 15456935 OWN - NLM STAT- MEDLINE DCOM- 20050802 LR - 20181113 IS - 0895-8696 (Print) IS - 0895-8696 (Linking) VI - 24 IP - 2 DP - 2004 TI - SRC-1 is involved in the control of the gene expression of myelin protein Po. PG - 217-26 AB - Steroid receptor coactivator-1 (SRC-1) has a crucial role in many different biological effects mediated by nuclear receptors. However, in spite of its ubiquitous expression, there are no data regarding its possible involvement in nuclear receptor transcriptional activity at the level of the peripheral nervous system. We investigated whether this coactivator might have a role in the control of glycoprotein Po gene expression. This myelin protein is a specific product of Schwann cells, with a fundamental role in the maintenance and functionality of peripheral myelin. Po is known to be stimulated by progesterone and by its 5alpha-reduced metabolite, dihydroprogesterone (DHP), through the corresponding steroid receptor. To determine whether the effect exerted by DHP on Po mRNA levels could be affected by and therefore associated with altered levels of SRC-1, a mouse Schwann cell line was stably transfected to over- or underexpress this coactivator. We found that SRC-1 overexpressing cells are more responsive to Po mRNA induction by DHP, whereas the effect of the steroid is completely lost in SRC-1-deficient cells. Interestingly, SRC-1 levels are also positively correlated with Po gene expression independently of DHP exposure. Finally, DHP treatment increases not only Po but also SRC-1 mRNA levels. Altogether, these data indicate for the first time that in rat Schwann cells, SRC-1 plays a role in the regulation of one of the most typical proteins of peripheral myelin. FAU - Cavarretta, Ilaria Teresa Rita AU - Cavarretta IT AD - Department of Endocrinology and Center of Excellence on Neurodegenerative Diseases, University of Milan, 20133 Milan, Italy. FAU - Martini, Luciano AU - Martini L FAU - Motta, Marcella AU - Motta M FAU - Smith, Carolyn Louise AU - Smith CL FAU - Melcangi, Roberto Cosimo AU - Melcangi RC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Mol Neurosci JT - Journal of molecular neuroscience : MN JID - 9002991 RN - 0 (Myelin P0 Protein) RN - 0 (Receptors, Steroid) RN - 0 (Trans-Activators) RN - 0 (Transcription Factors) RN - 145-14-2 (20-alpha-Dihydroprogesterone) RN - EC 2.3.1.48 (Histone Acetyltransferases) RN - EC 2.3.1.48 (NCOA1 protein, human) RN - EC 2.3.1.48 (Ncoa1 protein, mouse) RN - EC 2.3.1.48 (Nuclear Receptor Coactivator 1) SB - IM MH - 20-alpha-Dihydroprogesterone/metabolism MH - Animals MH - Cells, Cultured MH - *Gene Expression Regulation MH - Histone Acetyltransferases MH - Humans MH - Male MH - Mice MH - Myelin P0 Protein/genetics/*metabolism MH - Nuclear Receptor Coactivator 1 MH - Rats MH - Receptors, Steroid/metabolism MH - Schwann Cells/cytology/physiology MH - Trans-Activators/genetics/*metabolism MH - Transcription Factors/genetics/*metabolism EDAT- 2004/10/01 05:00 MHDA- 2005/08/03 09:00 CRDT- 2004/10/01 05:00 PHST- 2004/01/21 00:00 [received] PHST- 2004/02/05 00:00 [accepted] PHST- 2004/10/01 05:00 [pubmed] PHST- 2005/08/03 09:00 [medline] PHST- 2004/10/01 05:00 [entrez] AID - JMN:24:2:217 [pii] AID - 10.1385/JMN:24:2:217 [doi] PST - ppublish SO - J Mol Neurosci. 2004;24(2):217-26. doi: 10.1385/JMN:24:2:217.