Regulation of estradiol biosynthesis via prostaglandin-cAMP signalling

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Description

The rate-limiting step of steroid biosynthesis is the transfer of cholesterol from the cytosol into the mitochondrion across the outer mitochondrial membrane (OMM). Inside the mitochondrion, cholesterol is converted into pregnenolone that is then converted into estradiol in a four-step process. The transfer of cholesterol across the OMM is facilitated by the steroidogenic acute regulatory (STAR) protein. Endometriosis is associated with high production of ovarian steroids caused by high expression of STAR in endometrial tissue. Prostaglandin E2 acts through the EP2 receptor and raises cAMP. Protein kinase A phosphorylates the transcription factor CREB, and the coactivator CRTC2 moves into the nucleus. CRTC2 binds the bZIP domain of CREB whether or not CREB is phosphorylated, and the two together activate the STAR promoter. The map shows this regulation in endometriotic stromal cells.

References

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Contributors

Hanna Borlinghaus1, Falk Schreiber1,2, John Albanese3

Affiliations
  1. 1University of Konstanz, Konstanz, Germany
  2. 2Faculty of Information Technology, Monash University, Clayton, Australia
  3. 3University of Connecticut School of Medicine, Farmington, USA