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STMN1 Promotes Progesterone Production Via StAR Up-regulation in Mouse Granulosa Cells.

Abstract
Stathmin 1 (STMN1) is a biomarker in several types of neoplasms. It plays an important role in cell cycle progression, mitosis, signal transduction and cell migration. In ovaries, STMN1 is predominantly expressed in granulosa cells (GCs). However, little is known about the role of STMN1 in ovary. In this study, we demonstrated that STMN1 is overexpressed in GCs in patients with polycystic ovary syndrome (PCOS). In mouse primary GCs, the overexpression of STMN1 stimulated progesterone production, whereas knockdown of STMN1 decreased progesterone production. We also found that STMN1 positively regulates the expression of Star (steroidogenic acute regulatory protein) and Cyp11a1 (cytochrome P450 family 11 subfamily A member 1). Promoter and ChIP assays indicated that STMN1 increased the transcriptional activity of Star and Cyp11a1 by binding to their promoter regions. The data suggest that STMN1 mediates the progesterone production by modulating the promoter activity of Star and Cyp11a1. Together, our findings provide novel insights into the molecular mechanisms of STMN1 in ovary GC steroidogenesis. A better understanding of this potential interaction between STMN1 and Star in progesterone biosynthesis in GCs will facilitate the discovery of new therapeutic targets in PCOS.
AuthorsYun-De Dou, Han Zhao, Tao Huang, Shi-Gang Zhao, Xiao-Man Liu, Xiao-Chen Yu, Zeng-Xiang Ma, Yu-Chao Zhang, Tao Liu, Xuan Gao, Lei Li, Gang Lu, Wai-Yee Chan, Fei Gao, Hong-Bin Liu, Zi-Jiang Chen
JournalScientific reports (Sci Rep) Vol. 6 Pg. 26691 (06 08 2016) ISSN: 2045-2322 [Electronic] England
PMID27270953 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Phosphoproteins
  • STMN1 protein, human
  • Stathmin
  • Stmn1 protein, mouse
  • steroidogenic acute regulatory protein
  • Progesterone
  • Cholesterol Side-Chain Cleavage Enzyme
Topics
  • Animals
  • Cholesterol Side-Chain Cleavage Enzyme (metabolism)
  • Female
  • Granulosa Cells (metabolism, pathology)
  • Humans
  • Macaca mulatta
  • Mice
  • Phosphoproteins (biosynthesis)
  • Polycystic Ovary Syndrome (metabolism, pathology)
  • Progesterone (biosynthesis)
  • Stathmin (metabolism)
  • Up-Regulation

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