title: MCL1 is a key regulator of steroidogenesis in mouse Leydig cells.
abstract: Myeloid cell leukemia-1 (MCL1), an anti-apoptotic member of the BCL2 family, is expressed abundantly in the testis. Previous characterization revealed that MCL1 is expressed exclusively in the Leydig cells in the mouse testis, yet what it does in these cells remains unknown. We therefore analyzed testosterone biosynthesis in isolated primary Leydig cells and the MA-10 cell line, in which MCL1 was knocked down using an siRNA strategy. The mRNA abundance of the steroidogenic genes Star, Cyp11a1, Cyp17a1, Hsd3b1, Srd5a, and the luteinizing hormone/choriogonadotropin receptor Lhcgr were significantly reduced following MCL1 knockdown. Of the two enzymes required for testosterone biosynthesis, STAR and P450 SCC (encoded by Cyp11a1) enzyme abundance was also reduced following Mcl1 siRNA treatment, possibly leading to the reduced production of sex steroid precursors, and testosterone in these knockdown cells. Despite its classification as an anti-apoptosis protein, Mcl1 siRNA treatment did not affect cell survival. Collectively, our findings indicate that MCL1 plays a pivotal role in Leydig-cell steroidogenesis, and might provide novel insights into metabolic regulation in this cell. Mol. Reprod. Dev. 83: 226-235, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: First Affiliated Hospital of Guangxi Medical University, Guangxi, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Guang-Yu
authors.affiliation: Oncological Internal Medicine, People's Hospital of Guangxi Zhuang Automous Region, Guangxi, P. R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Hai-Yan
authors.affiliation: First Affiliated Hospital of Guangxi Medical University, Guangxi, P. R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ji-Hong
authors.affiliation: First Affiliated Hospital of Guangxi Medical University, Guangxi, P. R. China.
authors.forename: Mo
authors.initials: M
authors.lastname: Yun-Cong
authors.affiliation: First Affiliated Hospital of Guangxi Medical University, Guangxi, P. R. China.
authors.forename: Deng
authors.initials: D
authors.lastname: Xue-Lian
authors.affiliation: First Affiliated Hospital of Guangxi Medical University, Guangxi, P. R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chun-Yu
authors.affiliation: First Affiliated Hospital of Guangxi Medical University, Guangxi, P. R. China.
authors.forename: Su
authors.initials: S
authors.lastname: Wen-Yong
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D000072478:Cytochrome P450 Family 17 / Q000235:genetics / Q000378:metabolism; D007985:Leydig Cells; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011375:Progesterone Reductase / Q000235:genetics / Q000378:metabolism; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism; D013251:Steroid Isomerases / Q000235:genetics / Q000378:metabolism; D013256:Steroids / Q000378:metabolism*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; C579094:Mcl1 protein, mouse; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010750:Phosphoproteins; D011974:Receptors, LH; D013256:Steroids; D000098682:Steroidogenic Acute Regulatory Protein; D011375:Progesterone Reductase; D000072478:Cytochrome P450 Family 17; D002786:Cholesterol Side-Chain Cleavage Enzyme; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C518406:Srd5a1 protein, mouse; D013251:Steroid Isomerases