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Role of the steroidogenic acute regulatory protein in health and disease

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Abstract

Steroid hormones are an important class of regulatory molecules that are synthesized in steroidogenic cells of the adrenal, ovary, testis, placenta, brain, and skin, and influence a spectrum of developmental and physiological processes. The steroidogenic acute regulatory protein (STAR) predominantly mediates the rate-limiting step in steroid biosynthesis, i.e., the transport of the substrate of all steroid hormones, cholesterol, from the outer to the inner mitochondrial membrane. At the inner membrane, cytochrome P450 cholesterol side chain cleavage enzyme cleaves the cholesterol side chain to form the first steroid, pregnenolone, which is converted by a series of enzymes to various steroid hormones in specific tissues. Both basic and clinical evidence have demonstrated the crucial involvement of the STAR protein in the regulation of steroid biosynthesis. Multiple levels of regulation impinge on STAR action. Recent findings demonstrate that hormone-sensitive lipase, through its action on the hydrolysis of cholesteryl esters, plays an important role in regulating STAR expression and steroidogenesis which involve the liver X receptor pathway. Activation of the latter influences macrophage cholesterol efflux that is a key process in the prevention of atherosclerotic cardiovascular disease. Appropriate regulation of steroid hormones is vital for proper functioning of many important biological activities, which are also paramount for geriatric populations to live longer and healthier. This review summarizes the current level of understanding on tissue-specific and hormone-induced regulation of STAR expression and steroidogenesis, and provides insights into a number of cholesterol and/or steroid coupled physiological and pathophysiological consequences.

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Acknowledgments

The authors would like to thank many co-workers and collaborators, and the studies of several research groups whose contributions helped in preparing this review. The cooperation of the Clinical Research Institute at Texas Tech University Health Sciences Center is greatly appreciated. This review was supported, in part, by NIH Grants CA155223 to KP and, AR052190, 1R01AR056666-01A2, and R21AR066505-01A1 to ATS.

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  1. Department of Immunology and Molecular Microbiology, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA

    Pulak R. Manna & Kevin Pruitt

  2. Department of Dermatology, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA

    Cloyce L. Stetson

  3. Department of Dermatology, VA Medical Center, University of Alabama Birmingham, Birmingham, AL, 35294, USA

    Andrzej T. Slominski

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  1. Pulak R. Manna
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Correspondence to Pulak R. Manna.

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Manna, P.R., Stetson, C.L., Slominski, A.T. et al. Role of the steroidogenic acute regulatory protein in health and disease. Endocrine 51, 7–21 (2016). https://doi.org/10.1007/s12020-015-0715-6

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