Skip to main content

Advertisement

SpringerLink
Log in

SF-1 deficiency causes lipid accumulation in Leydig cells via suppression of STAR and CYP11A1

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Genetic mutations of steroidogenic factor 1 (also known as Ad4BP or Nr5a1) have increasingly been reported in patients with 46,XY disorders of sex development (46,XY disorders of sex development). However, because the phenotype of 46,XY disorders of sex development with a steroidogenic factor 1 mutation is wide-ranging, its precise diagnosis remains a clinical problem. We previously reported the frequent occurrence of lipid accumulation in Leydig cells among patients with 46,XY disorders of sex development with a steroidogenic factor 1 mutation, an observation also reported by other authors. To address the mechanism of lipid accumulation in this disease, we examined the effects of steroidogenic factor 1 deficiency on downstream targets of steroidogenic factor 1 in in vitro and in vivo. We found that lipid accumulation in Leydig cells was enhanced after puberty in heterozygous steroidogenic factor 1 knockout mice compared with wild-type mice, and was accompanied by a significant decrease in steroidogenic acute regulatory protein and CYP11A1 expression. In mouse Leydig cell lines, steroidogenic factor 1 knockdown induced a remarkable accumulation of neutral lipids and cholesterol with reduced androgen levels. Steroidogenic factor 1 knockdown reduced the expression of steroidogenic acute regulatory protein and CYP11A1, both of which are transcriptional targets of steroidogenic factor 1 and key molecules for steroidogenesis from cholesterol in the mitochondria. Knockdown of either steroidogenic acute regulatory protein or CYP11A1 also induced lipid accumulation, and knockdown of both had an additive effect. Our data suggested that lipid accumulation in the Leydig cells of the 46,XY disorders of sex development phenotype with a steroidogenic factor 1 mutation is due, at least in part, to the suppression of steroidogenic acute regulatory protein and CYP11A1, and a resulting increase in unmetabolized cholesterol.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. S. Erdogan, C. Kara, A. Ucakturk, M. Aydin, Etiological classification and clinical assessment of children and adolescents with disorders of sex development. J. Clin. Res. Pediatr. Endocrinol. 3(2), 77–83 (2011). doi:10.4274/jcrpe.v3i2.16

    Article  PubMed  PubMed Central  Google Scholar 

  2. D.A. Rice, A.R. Mouw, A.M. Bogerd, K.L. Parker, A shared promoter element regulates the expression of three steroidogenic enzymes. Mol. Endocrinol. 5(10), 1552–1561 (1991). doi:10.1210/mend-5-10-1552

    Article  CAS  PubMed  Google Scholar 

  3. K. Morohashi, S. Honda, Y. Inomata, H. Handa, T. Omura, A common trans-acting factor, Ad4-binding protein, to the promoters of steroidogenic P-450s. J. Biol. Chem. 267(25), 17913–17919 (1992).

  4. L. Lin, J.C. Achermann, Steroidogenic factor-1 (SF-1, Ad4BP, NR5A1) and disorders of testis development. Sex. Dev. 2(4-5), 200–209 (2008). doi:10.1159/000152036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. B. Ferraz-de-Souza, L. Lin, J.C. Achermann, Steroidogenic factor-1 (SF-1, NR5A1) and human disease. Mol. Cell. Endocrinol. 336(1-2), 198–205 (2011). doi:10.1016/j.mce.2010.11.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. E.A. Hoivik, A.E. Lewis, L. Aumo, M. Bakke, Molecular aspects of steroidogenic factor 1 (SF-1). Mol. Cell. Endocrinol. 315(1-2), 27–39 (2010). doi:10.1016/j.mce.2009.07.003

    Article  CAS  PubMed  Google Scholar 

  7. K.L. Parker, D.A. Rice, D.S. Lala, Y. Ikeda, X. Luo, M. Wong, M. Bakke, L. Zhao, C. Frigeri, N.A. Hanley, N. Stallings, B.P. Schimmer, Steroidogenic factor 1: an essential mediator of endocrine development. Recent Prog. Horm. Res. 57, 19–36 (2002)

    Article  CAS  PubMed  Google Scholar 

  8. X. Luo, Y. Ikeda, K.L. Parker, A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation. Cell 77(4), 481–490 (1994)

    Article  CAS  PubMed  Google Scholar 

  9. K.I. Morohashi, T. Omura, Ad4BP/SF-1, a transcription factor essential for the transcription of steroidogenic cytochrome P450 genes and for the establishment of the reproductive function. FASEB J. 10(14), 1569–1577 (1996)

    CAS  PubMed  Google Scholar 

  10. S.F. Ahmed, A. Bashamboo, A. Lucas-Herald, K. McElreavey, Understanding the genetic aetiology in patients with XY DSD. Br. Med. Bull. 106, 67–89 (2013). doi:10.1093/bmb/ldt008

  11. L. Lin, P. Philibert, B. Ferraz-de-Souza, D. Kelberman, T. Homfray, A. Albanese, V. Molini, N.J. Sebire, S. Einaudi, G.S. Conway, I.A. Hughes, J.L. Jameson, C. Sultan, M.T. Dattani, J.C. Achermann, Heterozygous missense mutations in steroidogenic factor 1 (SF1/Ad4BP, NR5A1) are associated with 46,XY disorders of sex development with normal adrenal function. J. Clin. Endocrinol. Metab. 92(3), 991–999 (2007). doi:10.1210/jc.2006-1672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. K. Sarafoglou, S.F. Ahmed, Disorders of sex development: challenges for the future. J. Clin. Endocrinol. Metab. 97(7), 2292–2294 (2012). doi:10.1210/jc.2012-2178

    Article  CAS  PubMed  Google Scholar 

  13. J.C. Achermann, M. Ito, M. Ito, P.C. Hindmarsh, J.L. Jameson, A mutation in the gene encoding steroidogenic factor-1 causes XY sex reversal and adrenal failure in humans. Nat. Genet. 22(2), 125–126 (1999). doi:10.1038/9629

    Article  CAS  PubMed  Google Scholar 

  14. B. Kohler, L. Lin, B. Ferraz-de-Souza, P. Wieacker, P. Heidemann, V. Schroder, H. Biebermann, D. Schnabel, A. Gruters, J.C. Achermann, Five novel mutations in steroidogenic factor 1 (SF1, NR5A1) in 46,XY patients with severe underandrogenization but without adrenal insufficiency. Hum. Mutat. 29(1), 59–64 (2008). doi:10.1002/humu.20588

    Article  PubMed  PubMed Central  Google Scholar 

  15. J.Y. Wu, I.N. McGown, L. Lin, J.C. Achermann, M. Harris, D.M. Cowley, S. Aftimos, K.A. Neville, C.S. Choong, A.M. Cotterill, A novel NR5A1 variant in an infant with elevated testosterone from an Australasian cohort of 46,XY patients with disorders of sex development. Clin. Endocrinol. 78(4), 545–550 (2013). doi:10.1111/cen.12012

    Article  CAS  Google Scholar 

  16. A. Ropke, A.C. Tewes, J. Gromoll, S. Kliesch, P. Wieacker, F. Tuttelmann, Comprehensive sequence analysis of the NR5A1 gene encoding steroidogenic factor 1 in a large group of infertile males. Eur. J. Hum. Genet. 21(9), 1012–1015 (2013). doi:10.1038/ejhg.2012.290

    Article  PubMed  PubMed Central  Google Scholar 

  17. B. Kohler, L. Lin, I. Mazen, C. Cetindag, H. Biebermann, I. Akkurt, R. Rossi, O. Hiort, A. Gruters, J.C. Achermann, The spectrum of phenotypes associated with mutations in steroidogenic factor 1 (SF-1, NR5A1, Ad4BP) includes severe penoscrotal hypospadias in 46,XY males without adrenal insufficiency. Eur. J. Endocrinol. 161(2), 237–242 (2009). doi:10.1530/EJE-09-0067

    Article  PubMed  PubMed Central  Google Scholar 

  18. M. Ono, V.R. Harley, Disorders of sex development: new genes, new concepts. Nature reviews. Endocrinology 9(2), 79–91 (2013). doi:10.1038/nrendo.2012.235

    CAS  PubMed  Google Scholar 

  19. D. Lin, T. Sugawara, J.F. Strauss 3rd, B.J. Clark, D.M. Stocco, P. Saenger, A. Rogol, W.L. Miller, Role of steroidogenic acute regulatory protein in adrenal and gonadal steroidogenesis. Science 267(5205), 1828–1831 (1995)

    Article  CAS  PubMed  Google Scholar 

  20. P. Jeyasuria, Y. Ikeda, S.P. Jamin, L. Zhao, D.G. De Rooij, A.P. Themmen, R.R. Behringer, K.L. Parker, Cell-specific knockout of steroidogenic factor 1 reveals its essential roles in gonadal function. Mol. Endocrinol. 18(7), 1610–1619 (2004). doi:10.1210/me.2003-0404

    Article  CAS  PubMed  Google Scholar 

  21. N. Camats, A.V. Pandey, M. Fernandez-Cancio, P. Andaluz, M. Janner, N. Toran, F. Moreno, A. Bereket, T. Akcay, E. Garcia-Garcia, M.T. Munoz, R. Gracia, M. Nistal, L. Castano, P.E. Mullis, A. Carrascosa, L. Audi, C.E. Fluck, Ten novel mutations in the NR5A1 gene cause disordered sex development in 46,XY and ovarian insufficiency in 46,XX individuals. J. Clin. Endocrinol. Metab. 97(7), E1294–1306 (2012). doi:10.1210/jc.2011-3169

    Article  CAS  PubMed  Google Scholar 

  22. N. Nishina-Uchida, R. Fukuzawa, C. Numakura, A.S. Suwanai, T. Hasegawa, Y. Hasegawa, Characteristic testicular histology is useful for the identification of NR5A1 gene mutations in prepubertal 46,XY patients. Horm. Res. Paediatr. 80(2), 119–128 (2013). doi:10.1159/000353763

    Article  CAS  PubMed  Google Scholar 

  23. M. Ascoli, Characterization of several clonal lines of cultured Leydig tumor cells: gonadotropin receptors and steroidogenic responses. Endocrinology 108(1), 88–95 (1981). doi:10.1210/endo-108-1-88

    Article  CAS  PubMed  Google Scholar 

  24. K. Shinoda, H. Lei, H. Yoshii, M. Nomura, M. Nagano, H. Shiba, H. Sasaki, Y. Osawa, Y. Ninomiya, O. Niwa et al.. Developmental defects of the ventromedial hypothalamic nucleus and pituitary gonadotroph in the Ftz-F1 disrupted mice. Dev. Dyn. 204(1), 22–29 (1995). doi:10.1002/aja.1002040104

    Article  CAS  PubMed  Google Scholar 

  25. J.J. Tremblay, R.S. Viger, A mutated form of steroidogenic factor 1 (SF-1 G35E) that causes sex reversal in humans fails to synergize with transcription factor GATA-4. J. Biol. Chem. 278(43), 42637–42642 (2003). doi:10.1074/jbc.M305485200

    Article  CAS  PubMed  Google Scholar 

  26. H. Yagi, M. Takagi, M. Kon, M. Igarashi, M. Fukami, Y. Hasegawa, Fertility preservation in a family with a novel NR5A1 mutation. Endocrine (2014).

  27. L.K. Christenson, J.F. Strauss, 3rd: Steroidogenic acute regulatory protein: an update on its regulation and mechanism of action. Arch. Med. Res. 32(6), 576–586 (2001)

    Article  CAS  PubMed  Google Scholar 

  28. M. Ito, J.C. Achermann, J.L. Jameson, A naturally occurring steroidogenic factor-1 mutation exhibits differential binding and activation of target genes. J. Biol. Chem. 275(41), 31708–31714 (2000). doi:10.1074/jbc.M002892200

    Article  CAS  PubMed  Google Scholar 

  29. M.C. Hu, N.C. Hsu, C.I. Pai, C.K. Wang, B. Chung, Functions of the upstream and proximal steroidogenic factor 1 (SF-1)-binding sites in the CYP11A1 promoter in basal transcription and hormonal response. Mol. Endocrinol. 15(5), 812–818 (2001). doi:10.1210/mend.15.5.0636

    Article  CAS  PubMed  Google Scholar 

  30. T. Baba, H. Otake, T. Sato, K. Miyabayashi, Y. Shishido, C.Y. Wang, Y. Shima, H. Kimura, M. Yagi, Y. Ishihara, S. Hino, H. Ogawa, M. Nakao, T. Yamazaki, D. Kang, Y. Ohkawa, M. Suyama, B.C. Chung, K. Morohashi, Glycolytic genes are targets of the nuclear receptor Ad4BP/SF-1. Nat. Commun. 5, 3634 (2014). doi:10.1038/ncomms4634

    Article  CAS  PubMed  Google Scholar 

  31. M. Ono, K. Kashimada, K. Miyai, T. Onishi, M. Takagi, S. Honma, S. Mizutani, In Vitro Enzyme Assay of CYP21A2 Mutation (R483Q) by A Novel Method Using Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry (LC-ESI-MS/MS). Clin. Pediatr. Endocrinol. 17(2), 49–56 (2008). doi:10.1297/cpe.17.49

    Article  PubMed  PubMed Central  Google Scholar 

  32. L.J. Martin, J.J. Tremblay, Nuclear receptors in Leydig cell gene expression and function. Biol. Reprod. 83(1), 3–14 (2010). doi:10.1095/biolreprod.110.083824

    Article  CAS  PubMed  Google Scholar 

  33. W.Y. Chen, J.H. Weng, C.C. Huang, B.C. Chung, Histone deacetylase inhibitors reduce steroidogenesis through SCF-mediated ubiquitination and degradation of steroidogenic factor 1 (NR5A1). Mol. Cell. Biol. 27(20), 7284–7290 (2007). doi:10.1128/MCB.00476-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. A.L. Del Tredici, C.B. Andersen, E.A. Currier, S.R. Ohrmund, L.C. Fairbain, B.W. Lund, N. Nash, R. Olsson, F. Piu, Identification of the first synthetic steroidogenic factor 1 inverse agonists: pharmacological modulation of steroidogenic enzymes. Mol. Pharmacol. 73(3), 900–908 (2008). doi:10.1124/mol.107.040089

    Article  PubMed  Google Scholar 

  35. M. Doghman, T. Karpova, G.A. Rodrigues, M. Arhatte, J. De Moura, L.R. Cavalli, V. Virolle, P. Barbry, G.P. Zambetti, B.C. Figueiredo, L.L. Heckert, E. Lalli, Increased steroidogenic factor-1 dosage triggers adrenocortical cell proliferation and cancer. Mol. Endocrinol. 21(12), 2968–2987 (2007). doi:10.1210/me.2007-0120

    Article  CAS  PubMed  Google Scholar 

  36. P.Y. Lai, C.Y. Wang, W.Y. Chen, Y.H. Kao, H.M. Tsai, T. Tachibana, W.C. Chang, B.C. Chung, Steroidogenic Factor 1 (NR5A1) resides in centrosomes and maintains genomic stability by controlling centrosome homeostasis. Cell death Differ. 18(12), 1836–1844 (2011). doi:10.1038/cdd.2011.54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. H.S. Bose, T. Sugawara, J.F. Strauss 3rd, W.L. Miller, International Congenital Lipoid Adrenal Hyperplasia, C.: The pathophysiology and genetics of congenital lipoid adrenal hyperplasia. N. Engl. J. Med. 335(25), 1870–1878 (1996). doi:10.1056/NEJM199612193352503

    Article  CAS  PubMed  Google Scholar 

  38. M. Aya, T. Ogata, A. Sakaguchi, S. Sato, N. Matsuo, Testicular histopathology in congenital lipoid adrenal hyperplasia: a light and electron microscopic study. Horm. Res. 47(3), 121–125 (1997)

    Article  CAS  PubMed  Google Scholar 

  39. S.O. Kim, C. Choi, C.J. Kim, J.S. Kim, D. Kwon, T.W. Kang, K. Park, S.B. Ryu, S.I. Jung, K.J. Oh, C.M. Im, Lipoid congenital adrenal hyperplasia: pathologic features of the testis. Urology 75(1), 176–178 (2010). doi:10.1016/j.urology.2009.04.073

    Article  PubMed  Google Scholar 

  40. T. Yamaguchi, N. Fujikawa, S. Nimura, Y. Tokuoka, S. Tsuda, T. Aiuchi, R. Kato, T. Obama, H. Itabe, Characterization of lipid droplets in steroidogenic MLTC-1 Leydig cells: Protein profiles and the morphological change induced by hormone stimulation. Biochim. Biophys. Acta. 1851(10), 1285–1295 (2015). doi:10.1016/j.bbalip.2015.06.007

    Article  CAS  PubMed  Google Scholar 

  41. K.M. Caron, S.C. Soo, W.C. Wetsel, D.M. Stocco, B.J. Clark, K.L. Parker, Targeted disruption of the mouse gene encoding steroidogenic acute regulatory protein provides insights into congenital lipoid adrenal hyperplasia. Proc. Natl. Acad. Sci. U.S.A. 94(21), 11540–11545 (1997)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. T. Hasegawa, L. Zhao, K.M. Caron, G. Majdic, T. Suzuki, S. Shizawa, H. Sasano, K.L. Parker, Developmental roles of the steroidogenic acute regulatory protein (StAR) as revealed by StAR knockout mice. Mol. Endocrinol. 14(9), 1462–1471 (2000). doi:10.1210/mend.14.9.0515

    Article  CAS  PubMed  Google Scholar 

  43. M.C. Hu, N.C. Hsu, N.B. El Hadj, C.I. Pai, H.P. Chu, C.K. Wang, B.C. Chung, Steroid deficiency syndromes in mice with targeted disruption of Cyp11a1. Mol. Endocrinol. 16(8), 1943–1950 (2002). doi:10.1210/me.2002-0055

    Article  CAS  PubMed  Google Scholar 

  44. N.M. Al-Saffar, J.C. Titley, D. Robertson, P.A. Clarke, L.E. Jackson, M.O. Leach, S.M. Ronen, Apoptosis is associated with triacylglycerol accumulation in Jurkat T-cells. Br. J. Cancer 86(6), 963–970 (2002). doi:10.1038/sj.bjc.6600188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. J. Boren, K.M. Brindle, Apoptosis-induced mitochondrial dysfunction causes cytoplasmic lipid droplet formation. Cell Death Differ. 19(9), 1561–1570 (2012). doi:10.1038/cdd.2012.34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. C.Y. Wang, W.Y. Chen, P.Y. Lai, B.C. Chung, Distinct functions of steroidogenic factor-1 (NR5A1) in the nucleus and the centrosome. Mol. Cell. Endocrinol. 371(1-2), 148–153 (2013). doi:10.1016/j.mce.2012.11.019

    Article  CAS  PubMed  Google Scholar 

  47. J. Malikova, N. Camats, M. Fernandez-Cancio, K. Heath, I. Gonzalez, M. Caimari, M. del Campo, M. Albisu, S. Kolouskova, L. Audi, C.E. Fluck, Human NR5A1/SF-1 mutations show decreased activity on BDNF (brain-derived neurotrophic factor), an important regulator of energy balance: testing impact of novel SF-1 mutations beyond steroidogenesis. PloS one 9(8), e104838 (2014). doi:10.1371/journal.pone.0104838

    Article  PubMed  PubMed Central  Google Scholar 

  48. M.A. Pianovski, L.R. Cavalli, B.C. Figueiredo, S.C. Santos, M. Doghman, R.C. Ribeiro, A.G. Oliveira, E. Michalkiewicz, G.A. Rodrigues, G. Zambetti, B.R. Haddad, E. Lalli, SF-1 overexpression in childhood adrenocortical tumours. Eur. J. Cancer 42(8), 1040–1043 (2006). doi:10.1016/j.ejca.2006.01.022

    Article  CAS  PubMed  Google Scholar 

  49. S. Sbiera, S. Schmull, G. Assie, H.U. Voelker, L. Kraus, M. Beyer, B. Ragazzon, F. Beuschlein, H.S. Willenberg, S. Hahner, W. Saeger, J. Bertherat, B. Allolio, M. Fassnacht, High diagnostic and prognostic value of steroidogenic factor-1 expression in adrenal tumors. J. Clin. Endocrinol. Metab. 95(10), E161–171 (2010). doi:10.1210/jc.2010-0653

    Article  CAS  PubMed  Google Scholar 

  50. S.R. Lewis, C.J. Hedman, T. Ziegler, W.A. Ricke, J.S. Jorgensen, Steroidogenic factor 1 promotes aggressive growth of castration-resistant prostate cancer cells by stimulating steroid synthesis and cell proliferation. Endocrinology 155(2), 358–369 (2014). doi:10.1210/en.2013-1583

    Article  CAS  PubMed  Google Scholar 

  51. S. Sbiera, E. Leich, G. Liebisch, I. Sbiera, A. Schirbel, L. Wiemer, S. Matysik, C. Eckhardt, F. Gardill, A. Gehl, S. Kendl, I. Weigand, M. Bala, C.L. Ronchi, T. Deutschbein, G. Schmitz, A. Rosenwald, B. Allolio, M. Fassnacht, M. Kroiss, Mitotane Inhibits Sterol-O-Acyl Transferase 1 Triggering Lipid-Mediated Endoplasmic Reticulum Stress and Apoptosis in Adrenocortical Carcinoma Cells. Endocrinology 156(11), 3895–3908 (2015). doi:10.1210/en.2015-1367

    Article  CAS  PubMed  Google Scholar 

  52. J.P. Suntharalingham, F. Buonocore, A.J. Duncan, J.C. Achermann, DAX-1 (NR0B1) and steroidogenic factor-1 (SF-1, NR5A1) in human disease. Best practice & research. Clin. Endocrinol. Metab. 29(4), 607–619 (2015). doi:10.1016/j.beem.2015.07.004

    CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Dr. Ikuo Kawashima and other lab members (Tokyo Metropolitan Institute of Medical Science) for technical assistance. We also thank Ms. Michiko Imanishi (Tokyo Metropolitan Institute of Medical Science) for technical assistant with histochemistry of mouse tissue. We are also indebted to Mr. James R. Valera for his help in editing the English manuscript.

Author contributions

M.H., T.M., Y.H., and F.S. conceived and designed the experiments. M.H, T.M., and T.O. performed the experiments. M.H. and T.M. analyzed the data. Y.H. and F.S. contributed reagents or analysis tools. M.H. and T.M. wrote and Y.H. proofread the paper.

Funding

This work was supported by grants from the Japan Society for the Promotion of Science KAKENHI, grant number 23659314 (to F.S.), and the Tokyo Metropolitan Government for the Tokyo Metropolitan Clinical Research Grant (2014A1-01).

Author information

Authors and Affiliations

  1. Department of Molecular Medical Research, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan

    Megumi Hatano, Toshiro Migita, Tomokazu Ohishi & Futoshi Shibasaki

  2. Division of Endocrinology and Metabolism, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan

    Megumi Hatano & Yukihiro Hasegawa

  3. Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan

    Megumi Hatano & Yoshihiro Ogawa

  4. Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan

    Toshiro Migita & Tomokazu Ohishi

  5. Institute of Microbial Chemistry (BIKAKEN), Numazu, Shizuoka, Japan

    Tomokazu Ohishi

  6. Department of Molecular Biology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Yuichi Shima & Ken-Ichirou Morohashi

Authors
  1. Megumi Hatano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Toshiro Migita
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tomokazu Ohishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuichi Shima
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yoshihiro Ogawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ken-Ichirou Morohashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yukihiro Hasegawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Futoshi Shibasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Toshiro Migita.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hatano, M., Migita, T., Ohishi, T. et al. SF-1 deficiency causes lipid accumulation in Leydig cells via suppression of STAR and CYP11A1. Endocrine 54, 484–496 (2016). https://doi.org/10.1007/s12020-016-1043-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-016-1043-1

Keywords

Search

Navigation