A potential role for zinc transporter 7 in testosterone synthesis in mouse Leydig tumor cells.
Previous studies have demonstrated that zinc (Zn) is an essential trace element which is involved in male reproduction. The zinc transporter (ZnT) family, SLC30a, is involved in the maintenance of Zn homeostasis and in mediating intracellular signaling events; however, relatively little is known regarding the effect of ZnTs on testosterone synthesis. Thus, in the present study, we aimed to determine the effect of Zn transporter 7 (ZnT7) on testosterone synthesis in male CD-1 mice and mouse Leydig cells. The findings of the present study revealed that the concentrations of Zn in the testes and Leydig cells were significantly lower in mice fed a Zn-deficient diet compared with the control mice fed a Zn-adequate diet. In addition, ZnT7 was principally expressed and colocalized with steroidogenic acute regulatory protein (StAR) in the Leydig cells of male CD-1 mice. ZnT7 expression was downregulated in the mice fed a Zn-deficient diet, which led to decreases in the expression of the enzymes involved in testosterone synthesis namely cholesterol side‑chain cleavage enzyme (P450scc) and 3β-hydroxysteroid dehydrogenase/D5-D4 isomerase (3β-HSD) as well as decreased serum testosterone levels. These results suggested that Znt7 may be involved in testosterone synthesis in the mouse testes. To examine this hypothesis, we used the mouse Leydig tumor cell line (MLTC-1 cell line) in which the ZnT7 gene had been silenced, in order to gauge the impact of changes in ZnT7 expression on testosterone secretion and the enzymes involved in testosterone synthesis. The results demonstrated that ZnT7 gene silencing downregulated the expression of StAR, P450scc and 3β-HSD as well as progesterone concentrations in the human chorionic gonadotrophin (hCG)-stimulated MLTC-1 cells. Taken together, these findings reveal that ZnT7 may play an important role in the regulation of testosterone synthesis by modulating steroidogenic enzymes, and may represent a therapeutic target in testosterone deficiency.
Department of Pathophysiology, China Medical University, Shenyang, Liaoning, P.R. China.
Qingqing
Q
Chu
Department of Pathophysiology, China Medical University, Shenyang, Liaoning, P.R. China.
Zhi-Hong
ZH
Chi
Department of Nephrology, Benxi Center Hospital, China Medical University, Benxi, Liaoning, P.R. China.
Xiuli
X
Zhang
Troops of 95935 Unit, Harbin, Heilongjiang, P.R. China.
Dan
D
Liang
School of Stomatology of China Medical University, Shenyang, Liaoning, P.R. China.
Xuemei
X
Wang
Department of Pathophysiology, China Medical University, Shenyang, Liaoning, P.R. China.
Yue
Y
Zhao
School of Stomatology of China Medical University, Shenyang, Liaoning, P.R. China.
Li
L
Zhang
Department of Histology and Embryology, Liaoning Medical College, Jinzhou, Liaoning, P.R. China.
Ping
P
Zhang
D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics* / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013739:Testosterone / Q000096:biosynthesis*; D015032:Zinc / Q000172:deficiency*; D000098682:Steroidogenic Acute Regulatory Protein
D027682:Cation Transport Proteins; D006063:Chorionic Gonadotropin; D010750:Phosphoproteins; D034741:RNA, Small Interfering; C472293:ZnT7 protein, mouse; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; D011374:Progesterone; D015096:3-Hydroxysteroid Dehydrogenases; D002786:Cholesterol Side-Chain Cleavage Enzyme; D015032:Zinc