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Molecular and Cellular Biochemistry

, Volume 433, Issue 1–2, pp 79–95 | Cite as

Steroidogenic genes expressions are repressed by high levels of leptin and the JAK/STAT signaling pathway in MA-10 Leydig cells

  • David A. Landry
  • François Sormany
  • Josée Haché
  • Pauline Roumaud
  • Luc J. MartinEmail author
Article

Abstract

The adipose tissue is an important endocrine organ secreting numerous peptide hormones, including leptin. Increased circulating levels of leptin, as a result of hormonal resistance in obese individuals, may contribute to lower androgen production in obese males. However, the molecular mechanisms involved need to be better defined. Androgens are mainly produced by Leydig cells within the testis. In male rodents, activation of the leptin receptor modulates a cascade of intracellular signal transduction pathways which may lead to regulation of transcription factors having influences on steroidogenesis in Leydig cells. Thus, as a result of high leptin levels interacting with its receptor and modulating the activity of the JAK/STAT signaling pathway, the activity of transcription factors important for steroidogenic genes expressions may be inhibited in Leydig cells. Here we show that Lepr is increasingly expressed within Leydig cells according to postnatal development. Although high levels of leptin (corresponding to obesity condition) alone had no effect on Leydig cells’ steroidogenic genes expression, it downregulated cAMP-dependent activations of the cholesterol transporter Star and of the rate-limiting steroidogenic enzyme Cyp11a1. Our results suggest that STAT transcriptional activity is downregulated by high levels of leptin, leading to reduced cAMP-dependent steroidogenic genes (Star and Cyp11a1) expressions in MA-10 Leydig cells. However, other transcription factors such as members of the SMAD and NFAT families may be involved and need further investigation to better define how leptin regulates their activities and their relevance for Leydig cells function.

Keywords

Leptin Lepr Ob-R Steroidogenesis Star Cyp11a1 Leydig cells 

Notes

Acknowledgements

We would like to thank Dr. Mario Ascoli for generously providing the MA-10 cell line used in this study. We are also grateful to Dr. Jacques J. Tremblay (Université Laval, Québec, Qc) for kindly providing plasmid constructs used in this study. This work was supported by the Natural Sciences and Engineering Research Council (NSERC) of Canada (#386557-2012 to L.J.M.), the New Brunswick Health Research Foundation (NBHRF) (#2010-SEED-178 and 2013-OG to L.J.M.), and the New Brunswick Innovation Foundation (NBIF) (#IAR2012 and IAR2013-029 to L.J.M.).

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest that would prejudice their impartiality.

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Authors and Affiliations

  1. 1.Department of BiologyUniversité de MonctonMonctonCanada

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