Regulation of estradiol biosynthesis via prostaglandin-mediated cAMP signalling in ovarian endometric stroma cells

Downloads:   GraphML   Annotated Map  

Contributors

Hanna Borlinghaus, Falk Schreiber, John Albanese (Annotation)

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.

References

  1. Stocco DM, Selvaraj V. Yet Another Scenario in the Regulation of the Steroidogenic Acute Regulatory (STAR) Protein Gene. Endocrinology. 2017 Feb 1;158(2):235-238. doi: 10.1210/en.2016-1874. PMID: 28430922.

  2. Xu JN, Zeng C, Zhou Y, Peng C, Zhou YF, Xue Q. Metformin inhibits StAR expression in human endometriotic stromal cells via AMPK-mediated disruption of CREB-CRTC2 complex formation. J Clin Endocrinol Metab. 2014 Aug;99(8):2795-803. doi: 10.1210/jc.2014-1593. PMID: 24823468.

  3. Wu MH, Lu CW, Chuang PC, Tsai SJ. Prostaglandin E2: the master of endometriosis? Exp Biol Med (Maywood). 2010 Jun;235(6):668-77. doi: 10.1258/ebm.2010.009321. PMID: 20511671.

  4. Sun HS, Hsiao KY, Hsu CC, Wu MH, Tsai SJ. Transactivation of steroidogenic acute regulatory protein in human endometriotic stromalcells is mediated by the prostaglandin EP2 receptor. Endocrinology. 2003 Sep;144(9):3934-42. PMID: 12933667.