A potential role for zinc transporter 7 in testosterone synthesis in mouse Leydig tumor cells

Abstract

Abstract. 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.

Combined Supplementation of Nano-Zinc Oxide and Thyme Oil Improves the Nutrient Digestibility and Reproductive Fertility in the Male Californian Rabbits

“…Therefore, supporting our results, coadministration of ZnO-NPs and THO synergistically increase the testosterone concentration rather than each alone. Two pathways could explain our findings; (a) testosterone synthesis from cholesterol induced by THO [20], or (a) endogenous molecular factors in the Leydig cells stimulated by the ZnO-NPs which require additional research and molecular studies [54]. The same pathway explains the increased secretion and volume of seminal plasma from the accessory genital glands which mainly depend on the testosterone secretion [56].…”

“…Accordingly, the blood cholesterol could be directed for the production of testosterone in agreement with our findings. Moreover, Zn concentrations in the Leydig cells were found to be significantly lowered in mice fed a Zn-deficient diet compared to controls, and that the zinc transporter-7 (ZnT7) was principally expressed in the Leydig cells ZnT7 which plays an important role in the regulation of testosterone synthesis by modulating the steroidogenic enzymes [54]. All above suggests that zinc could play a direct pivotal role on those testosterone-secreting cells which coincide with our findings for the highest increment of testosterone in response to ZnO-NPs supplementation.…”

Effect of shell as natural testosterone boosters in Sprague Dawley rats

“…Chu et al . [2] study on Leydig cells in mice found that Zn transporters (ZnT7) may play an important role in the regulation of testosterone synthesis by modulating steroidogenic (STARs) enzymes and may represent as therapeutic target in testosterone deficiency. In singing birds, testosterone levels influence the quality of sound and feathers.…”

Effect of zinc (Zn) supplementation on quality and quantity of striped catfish Pangasianodon hypophthalmus sperm

“…Zinc is also drawn in lipid catabolism which is the energy source for sperm to actively motile. In addition, zinc is also associated with testosterone secretion, so that it's undoubtedly required in male reproduction (Chu et al, 2016). The activity of ribonuclease enzyme also demanded zinc existence to process spermatogenesis, during spermatogenesis, and at the end of spermatogenesis (Widhyari et al, 2015).…”