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The Steroidogenic Acute Regulatory Protein (StAR)

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Cholesterol Transporters of the START Domain Protein Family in Health and Disease

Abstract

StAR, the Steroidogenic Acute Regulatory protein, was named for its critical role in the acute regulation of steroid hormone biosynthesis in the adrenal and gonads following tropic hormone stimulation. StAR synthesis is required for the first and rate-limiting step in steroid hormone biosynthesis, cholesterol transport into mitochondria. It was a long journey to finding the acute regulator of steroidogenesis, and this chapter provides a historical and personal account of this journey from the perspective of Dr. Douglas M. Stocco. Over the past two decades, we have gained significant insight into the mechanisms that regulate StAR expression, and into StAR structure and function. This chapter also provides a summary of the literature that has led to our current understanding of the cyclic adenosine-3′,5′-monophosphate (cAMP)-protein kinase A-dependent mechanisms that control StAR expression at the transcriptional and post-transcriptional levels in steroidogenic tissues.

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Abbreviations

AC:

adenylyl cyclase

ACTH:

adrenocorticotropic hormone

AMP:

adenosine-3′,5′-monophosphate

AP-1:

activator protein 1

AURE:

adenosine-uridine-rich destabilizing element

Bt2cAMP:

N6,2′-O-dibutyryl-adenosine-3′,5′-monophosphate

bZIP:

basic leucine zipper

cAMP:

cyclic AMP

CBP/p300:

CREB-binding protein

C/EBPβ:

CCAAT enhancer-binding protein-beta

COUP-TF:

chicken ovalbumin upstream promoter transcription factor I and II

CREB:

cyclic-AMP responsive element-binding protein

CREM:

CREB modulator protein

CRH:

corticotropin hormoneDAGdiacylglycerol

DAX-1:

dosage sensitive sex reversal-adrenal hypoplasia congenital gene on the X chromosome gene 1

ER:

endoplasmic reticulum

FSH:

follicule stimulating hormone

GnRH:

gonadotropin-releasing hormone

IP3:

inositol 1, 4, 5 trisphosphate

LH:

luteinizing hormone

NPC:

Niemann Pick type C

NUR77/NGFI-B:

nerve growth factor induced-B

PAP7:

TSPO associated protein 7 (ACBD3)

PIC:

preinitiation complex

PKA:

protein kinase A

PKC:

protein kinase C

Poly(A):

polyadenylation site

RNAPII:

ribonucleic acid polymerase II

SF1:

steroidogenic factor 1

StAR:

steroidogenic acute regulatory protein

START:

StAR-related lipid transfer domain

TSPO:

18 kDa translocator protein

TSS:

transcription start site

UTR:

untranslated region

VDAC1:

voltage-dependent anion channel

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Authors and Affiliations

  1. Department of Biochemistry & Molecular Biology, University of Louisville, 40292, Louisville, KY, USA

    Barbara J. Clark Ph.D.

  2. Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, 79430, Lubbock, TX, USA

    Douglas M. Stocco Ph.D.

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  1. Barbara J. Clark Ph.D.
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  1. Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, Kentucky, USA

    Barbara J. Clark

  2. Cell Biology and Biochemistry, Texas Tech Univ. Health Sciences Center, Lubbock, Texas, USA

    Douglas M. Stocco

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Clark, B., Stocco, D. (2014). The Steroidogenic Acute Regulatory Protein (StAR). In: Clark, B., Stocco, D. (eds) Cholesterol Transporters of the START Domain Protein Family in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1112-7_2

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