STMN1 Promotes Progesterone Production Via StAR Up-regulation in Mouse Granulosa Cells.
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.
Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China.|The Key laboratory for Reproductive Endocrinology of Ministry of Education, China.|Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
Yun-De
YD
Dou
Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China.|The Key laboratory for Reproductive Endocrinology of Ministry of Education, China.|Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
Han
H
Zhao
Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China.|The Key laboratory for Reproductive Endocrinology of Ministry of Education, China.|Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
Tao
T
Huang
Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China.|The Key laboratory for Reproductive Endocrinology of Ministry of Education, China.|Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
Shi-Gang
SG
Zhao
Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China.|The Key laboratory for Reproductive Endocrinology of Ministry of Education, China.|Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
Xiao-Man
XM
Liu
Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China.|The Key laboratory for Reproductive Endocrinology of Ministry of Education, China.|Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
Xiao-Chen
XC
Yu
Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China.|The Key laboratory for Reproductive Endocrinology of Ministry of Education, China.|Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
Zeng-Xiang
ZX
Ma
Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China.|The Key laboratory for Reproductive Endocrinology of Ministry of Education, China.|Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
Yu-Chao
YC
Zhang
Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China.|The Key laboratory for Reproductive Endocrinology of Ministry of Education, China.|Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
Tao
T
Liu
Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China.|The Key laboratory for Reproductive Endocrinology of Ministry of Education, China.|Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
Xuan
X
Gao
Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China.|The Key laboratory for Reproductive Endocrinology of Ministry of Education, China.|Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
Lei
L
Li
The Chinese University of Hong Kong-Shandong University Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
Gang
G
Lu
The Chinese University of Hong Kong-Shandong University Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
Wai-Yee
WY
Chan
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Fei
F
Gao
Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China.|The Key laboratory for Reproductive Endocrinology of Ministry of Education, China.|Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.|The Chinese University of Hong Kong-Shandong University Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
Hong-Bin
HB
Liu
Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.|National Research Center for Assisted Reproductive Technology and Reproductive Genetics, China.|The Key laboratory for Reproductive Endocrinology of Ministry of Education, China.|Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.|Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China.
Zi-Jiang
ZJ
Chen
D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D005260:Female; D006107:Granulosa Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008253:Macaca mulatta; D051379:Mice; D010750:Phosphoproteins / Q000096:biosynthesis*; D011085:Polycystic Ovary Syndrome / Q000378:metabolism / Q000473:pathology; D011374:Progesterone / Q000096:biosynthesis*; D050777:Stathmin / Q000378:metabolism*; D015854:Up-Regulation; D000098682:Steroidogenic Acute Regulatory Protein
D010750:Phosphoproteins; C493995:STMN1 protein, human; D050777:Stathmin; C493994:Stmn1 protein, mouse; D000098682:Steroidogenic Acute Regulatory Protein; D011374:Progesterone; D002786:Cholesterol Side-Chain Cleavage Enzyme