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Post-transcriptional and Post-translational Regulation of Steroidogenesis

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Post-transcriptional Mechanisms in Endocrine Regulation

Abstract

Steroid hormones are produced in the adrenal cortex, testis, ovary, placenta and some peripheral tissues such as adipose tissue and brain (neurosteroids). They play important roles in carbohydrate metabolism (glucocorticoids), mineral balance (mineralocorticoids) and reproductive functions (gonadal steroids). Steroids also play a role in several other cellular processes including inflammatory responses, stress responses, bone metabolism, cardiovascular fitness, behavior, cognition and mood. The process of biosynthesis of steroids, termed steroidogenesis is a multistep and multienzyme process which uses cholesterol as the common precursor for the production of all types of steroid hormones. The process can be broadly divided into four major segments: (a) cholesterol acquisition, (b) cholesterol mobilization from lipid droplets, (c) cholesterol transport to and from the mitochondrial outer membrane to the inner membrane for side-chain cleavage to pregnenolone, and (d) efflux of pregnenolone to the endoplasmic reticulum for the tissue specific production of various steroid hormones. Trophic hormones regulate these steps under both acute and chronic conditions. Many tissue specific transcriptional regulators, steroidogenic enzymes, as well as cholesterol transport protein, steroidogenic acute regulatory protein (StAR protein), coordinately regulate steroid hormone production. In recent years accumulating evidence suggests that post-transcriptional and post-translational regulatory events such as phosphorylation/dephosphorylation and protein–protein interactions also contribute significantly to the regulation of steroidogenesis. In addition, emerging evidence suggests the involvement of specific miRNAs in the regulation of both the acute and chronic steroidogenesis. This chapter summarizes the recent advances associated with the post-transcriptional and post-translational regulation of steroid hormone biosynthesis.

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Abbreviations

ACAT1:

Acyl-coenzyme A:cholesterol acyltransferase 1

ACTH:

Adrenocorticotropic hormone

AII:

Angiotensin II

ANC:

Adenine nucleotide transporter

AALO:

Allopregnanolone

CEH:

Neutral cholesteryl ester hydrolase

CE:

Cholesteryl ester

CEs:

Cholesteryl esters

ECD:

Extracellular domain

ER:

Endoplasmic reticulum

FRET:

Quantitative fluorescence resonance energy transfer

FSH:

Follicle-stimulating hormone

hCG:

Human chorionic gonadotropin

HDL:

High-density lipoprotein

HSL:

Hormone-sensitive lipase

IMM:

Inner mitochondrial membrane

LDL:

Low-density lipoprotein

LH:

Luteinizing hormone

OMM:

Outer mitochondrial membrane

NSF:

N-ethylmaleimide-sensitive factor

CYP11A1:

P450c11A

CYP11B1:

P450c11

CYP11B2:

Aldosterone synthase

CYP17:

P450c17

CYP21A2:

P450c21

PBR:

Peripheral-type benzodiazepine receptor

PDZ:

PSD-95, DglA, ZO-1

PKA:

cAMP-dependent protein kinase

SR-BI:

Scavenger receptor Class B, type I

StAR:

Steroidogenic acute regulatory protein

TSPO:

Translocator protein

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Acknowledgments

This work was supported by National Institutes of Health, NHLBI, Grant 2R01HL33881 and by the Office of Research and Development, Medical Service, Department of Veterans Affairs.

The authors are thankful to Mr. Kris Morrow, Medical Media, VA Palo Alto Health Care System for his assistance in the preparation of graphic illustration.

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Authors and Affiliations

  1. Geriatric Research, Education and Clinical Center (GRECC-182B), Veterans Affairs Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, CA, 94304, USA

    Wen-Jun Shen, Zhigang Hu, Jie Hu & Salman Azhar

  2. Division of Endocrinology, Stanford University, Stanford, CA, 94305, USA

    Wen-Jun Shen, Zhigang Hu & Fredric B. Kraemer

  3. Jiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Science, Nanjing Normal University, Nanjing, 210046, China

    Zhigang Hu

  4. Division of Gastroenterology and Hepatology, Stanford University, Stanford, CA, 94305, USA

    Salman Azhar

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  1. Wen-Jun Shen
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  2. Zhigang Hu
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  3. Jie Hu
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  4. Fredric B. Kraemer
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  5. Salman Azhar
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Correspondence to Salman Azhar .

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Editors and Affiliations

  1. Departments of Biological Chemistry & Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, MI, USA

    K.M.J. Menon, PhD

  2. Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, MI, USA

    Aaron Goldstrohm, PhD

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Shen, WJ., Hu, Z., Hu, J., Kraemer, F.B., Azhar, S. (2016). Post-transcriptional and Post-translational Regulation of Steroidogenesis. In: Menon, PhD, K., Goldstrohm, PhD, A. (eds) Post-transcriptional Mechanisms in Endocrine Regulation. Springer, Cham. https://doi.org/10.1007/978-3-319-25124-0_12

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