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SCAP/SREBP pathway is required for the full steroidogenic response to cyclic AMP

Shimizu-Albergine, Masami, Van Yserloo, Brian, Golkowski, Martin G., Ong, Shao-En, Beavo, Joseph A., Bornfeldt, Karin E.·2016·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1611424113
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Abstract

Significance: Luteinizing hormone stimulates production of testosterone and other steroids largely through a surge in the second messenger cAMP and subsequent activation of protein kinase A (PKA) in target cells. Rates of steroidogenesis are also dependent on the availability of cholesterol, a steroid building block. We propose, based on our results, that cAMP/PKA coordinates the functions of multiple pathways to regulate cellular cholesterol handling and synthesis and downstream steroid output. Activation of the cholesterol-sensing SCAP–SREBP2 pathway plays an important role in cAMP/PKA coordination of steroidogenesis. These cAMP/PKA-induced pathways are likely to be major regulators of sterol biosynthesis and cholesterol recharging in steroid hormone synthetic and other tissues. Cyclic nucleotide phosphodiesterases can be targeted to promote steroidogenesis and cholesterol metabolism.

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Metadata

Authors
Shimizu-Albergine, M., Van Yserloo, B., Golkowski, M. G., Ong, S.-E., Beavo, J. A., & Bornfeldt, K. E.
Affiliations
  • School of Medicine, Department of Pharmacology, University of Washington, Seattle, WA 98195;
  • School of Medicine, Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA 98109;
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2016-09-06
Volume
113
Issue
38
ISSN
  • 0027-8424
  • 1091-6490
DOI
10.1073/pnas.1611424113
Cited by
45
References
2
Language
en
Licence
www.pnas.org/site/misc/userlicense.xhtml (vor, 181 d)
Funders
NIH (R01GM083926, R01GM083926-02S1, R01HL062887, P01HL092969, R01HL126028, P30DK017047, S10 OD016240)

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