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SET/PP2A system regulates androgen production in ovarian follicles in vitro

Ling-Ling Gao1, Xiao-Qiang Liu, Bo-Qun Xu

  • 1The State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China. gaolingling86@gmail.com

Molecular and Cellular Endocrinology
|May 1, 2013
PubMed

Insights

The study reveals that SET protein stimulates testosterone production in ovarian theca cells by inhibiting PP2A phosphatase activity, ultimately enhancing P450c17 lyase activity.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Reproductive Biology

Background:

  • The SET protein plays diverse roles in cellular functions, including transcription and apoptosis.
  • In ovaries, SET is primarily found in theca cells and oocytes, suggesting a role in ovarian function.

Purpose of the Study:

  • To investigate the role of SET protein in regulating testosterone production in ovarian theca cells.
  • To elucidate the molecular mechanism by which SET influences testosterone biosynthesis, focusing on its interaction with protein phosphatase 2A (PP2A).

Main Methods:

  • SET protein expression was manipulated (overexpression and knockdown) in ovarian theca cells.
  • The activity of PP2A was modulated using inhibitors (okadaic acid) and activators.
  • The effect of SET and PP2A on the lyase activity of P450c17 was assessed.
  • RNA interference (siRNA) was used to knockdown PP2A.

Main Results:

  • SET overexpression in theca cells increased testosterone production, while SET knockdown decreased it.
  • SET negatively regulated PP2A activity; inhibiting PP2A (using okadaic acid) increased testosterone synthesis, while activation decreased it.
  • SET enhanced the lyase activity of P450c17, whereas PP2A inhibited this activity, confirming PP2A's role in SET-mediated testosterone regulation.

Conclusions:

  • SET initiates a pathway involving PP2A to regulate testosterone biosynthesis.
  • This pathway involves SET inhibiting PP2A activity, which in turn increases the lyase activity of P450c17, leading to enhanced testosterone production.

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