The role of Foxo3 in leydig cells

Young Suk Choi, Joo Eun Song, Byung Soo Kong, Jae Won Hong, Silvia Novelli, Eunjig Lee

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Purpose: Foxo3 in female reproduction has been reported to regulate proliferation of granulose cells that form follicles. There are no reports so far that discuss on the role of Foxo3 in males. This study was designed to outline the role of Foxo3 in the testes. Materials and Methods: Testes from mice at birth to postpartum week (PPW) 5 were isolated and examined for the expression of Foxo3 using immunostaining. To elucidate role of Foxo3 in Leydig cells, R2C cells were treated with luteinizing hormone (LH) and the phosphorylation of Foxo3. Testosterone and steroidogenic acute regulatory (StAR) protein levels were measured after constitutive active [triple mutant (TM)] human FOXO3 adenovirus was transduced and StAR promoter assay was performed. Results: Foxo3 expression in the testicles started from birth and lasted until PPW 3. After PPW 3, most Foxo3 expression occurred in the nuclei of Leydig cells; however, at PPW 5, Foxo3 was expressed in both the nucleus and cytoplasm. When R2C cells were treated with luteinizing hormone, Foxo3 phosphorylation levels by AKT increased. After blocking the PI3K pathway, LH-induced phosphorylated Foxo3 levels decreased, indicating that LH signaling regulates Foxo3 localization. When active FOXO3-TM adenovirus was introduced into a Leydig tumor cell line, the concentrations of testosterone and StAR protein decreased. When FOXO3 and a StAR promoter vector were co-transfected into HEK293 cells for a reporter assay, FOXO3 inhibited the StAR promoter. Conclusion: FOXO3 affects testosterone synthesis by inhibiting the formation of StAR protein. LH hormone, meanwhile, influences Foxo3 localization, mediating its function.

Original languageEnglish
Pages (from-to)1590-1596
Number of pages7
JournalYonsei medical journal
Volume56
Issue number6
DOIs
Publication statusPublished - 2015 Nov 1

Fingerprint

Leydig Cells
Luteinizing Hormone
Postpartum Period
Testosterone
Testis
Phosphorylation
Parturition
Human Adenoviruses
HEK293 Cells
Tumor Cell Line
Phosphatidylinositol 3-Kinases
Adenoviridae
Reproduction
Cytoplasm
Cell Proliferation
Hormones
steroidogenic acute regulatory protein

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Choi, Y. S., Song, J. E., Kong, B. S., Hong, J. W., Novelli, S., & Lee, E. (2015). The role of Foxo3 in leydig cells. Yonsei medical journal, 56(6), 1590-1596. https://doi.org/10.3349/ymj.2015.56.6.1590
Choi, Young Suk ; Song, Joo Eun ; Kong, Byung Soo ; Hong, Jae Won ; Novelli, Silvia ; Lee, Eunjig. / The role of Foxo3 in leydig cells. In: Yonsei medical journal. 2015 ; Vol. 56, No. 6. pp. 1590-1596.
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Choi, YS, Song, JE, Kong, BS, Hong, JW, Novelli, S & Lee, E 2015, 'The role of Foxo3 in leydig cells', Yonsei medical journal, vol. 56, no. 6, pp. 1590-1596. https://doi.org/10.3349/ymj.2015.56.6.1590

The role of Foxo3 in leydig cells. / Choi, Young Suk; Song, Joo Eun; Kong, Byung Soo; Hong, Jae Won; Novelli, Silvia; Lee, Eunjig.

In: Yonsei medical journal, Vol. 56, No. 6, 01.11.2015, p. 1590-1596.

Research output: Contribution to journalArticle

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N2 - Purpose: Foxo3 in female reproduction has been reported to regulate proliferation of granulose cells that form follicles. There are no reports so far that discuss on the role of Foxo3 in males. This study was designed to outline the role of Foxo3 in the testes. Materials and Methods: Testes from mice at birth to postpartum week (PPW) 5 were isolated and examined for the expression of Foxo3 using immunostaining. To elucidate role of Foxo3 in Leydig cells, R2C cells were treated with luteinizing hormone (LH) and the phosphorylation of Foxo3. Testosterone and steroidogenic acute regulatory (StAR) protein levels were measured after constitutive active [triple mutant (TM)] human FOXO3 adenovirus was transduced and StAR promoter assay was performed. Results: Foxo3 expression in the testicles started from birth and lasted until PPW 3. After PPW 3, most Foxo3 expression occurred in the nuclei of Leydig cells; however, at PPW 5, Foxo3 was expressed in both the nucleus and cytoplasm. When R2C cells were treated with luteinizing hormone, Foxo3 phosphorylation levels by AKT increased. After blocking the PI3K pathway, LH-induced phosphorylated Foxo3 levels decreased, indicating that LH signaling regulates Foxo3 localization. When active FOXO3-TM adenovirus was introduced into a Leydig tumor cell line, the concentrations of testosterone and StAR protein decreased. When FOXO3 and a StAR promoter vector were co-transfected into HEK293 cells for a reporter assay, FOXO3 inhibited the StAR promoter. Conclusion: FOXO3 affects testosterone synthesis by inhibiting the formation of StAR protein. LH hormone, meanwhile, influences Foxo3 localization, mediating its function.

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Choi YS, Song JE, Kong BS, Hong JW, Novelli S, Lee E. The role of Foxo3 in leydig cells. Yonsei medical journal. 2015 Nov 1;56(6):1590-1596. https://doi.org/10.3349/ymj.2015.56.6.1590