Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Mar:197:105506.
doi: 10.1016/j.jsbmb.2019.105506. Epub 2019 Oct 28.

The role of adrenal derived androgens in castration resistant prostate cancer

Monique Barnard  1 , Elahe A Mostaghel  2 , Richard J Auchus  3 , Karl-Heinz Storbeck  4
Affiliations
Review

The role of adrenal derived androgens in castration resistant prostate cancer

Monique Barnard et al. J Steroid Biochem Mol Biol. 2020 Mar.

Abstract

Castration resistant prostate cancer (CRPC) remains androgen dependant despite castrate levels of circulating testosterone following androgen deprivation therapy, the first line of treatment for advanced metstatic prostate cancer. CRPC is characterized by alterations in the expression levels of steroidgenic enzymes that enable the tumour to derive potent androgens from circulating adrenal androgen precursors. Intratumoral androgen biosynthesis leads to the localized production of both canonical androgens such as 5α-dihydrotestosterone (DHT) as well as less well characterized 11-oxygenated androgens, which until recently have been overlooked in the context of CRPC. In this review we discuss the contribution of both canonical and 11-oxygenated androgen precursors to the intratumoral androgen pool in CRPC. We present evidence that CRPC remains androgen dependent and discuss the alterations in steroidogenic enzyme expression and how these affect the various pathways to intratumoral androgen biosynthesis. Finally we summarize the current treatment strategies for targeting adrenal derived androgen biosynthesis.

Keywords: 11-ketotestosterone; 11-oxygenated androgens; 11β-hydroxyandrostenedione; Adrenal androgen precursors; Prostate cancer.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Schematic overview of adrenal androgen biosynthesis. Arrows are labelled with the catalyzing enzyme and isoform where appropriate. Potent androgens are shown in grey. Essential accessory proteins are also indicated: adrenodoxin (ADX); adrenodoxin reductase (ADXR); cytochrome b5 (b5); cytochrome P450 oxidoreductase (POR); hexose-6-phosphate dehydrogenase (H6PDH); PAPS synthase 2 (PAPSS2); steroidogenic acute regulatory protein (StAR).
Figure 2.
Figure 2.
Schematic overview of the intratumoral pathways converting circulating adenal androgen precursors to potent androgens. The relative circulating concentrations of adrenal androgens are indicated by the size of spheres (not to scale). Arrows are labelled with the catalyzing enzyme and isoform where appropriate with preferred reactions in the 5α-dione and 11OHA4 pathways shown with bold arrows. Potent androgens are shown in grey.
See this image and copyright information in PMC

References

    1. Heinlein CA, and Chang C (2004) Androgen receptor in prostate cancer. Endocr. Rev 25, 276–308 - PubMed
    1. Deslypere JP, Young M, Wilson JD, and McPhaul MJ (1992) Testosterone and 5 alpha-dihydrotestosterone interact differently with the androgen receptor to enhance transcription of the MMTV-CAT reporter gene. Mol. Cell. Endocrinol 88, 15–22 - PubMed
    1. Luu-The V, Bélanger A, and Labrie F (2008) Androgen biosynthetic pathways in the human prostate. Best Pract. Res. Clin. Endocrinol. Metab 22, 207–221 - PubMed
    1. Penning TM, Jin Y, Rizner TL, and Bauman DR (2008) Pre-receptor regulation of the androgen receptor. Mol. Cell. Endocrinol 281, 1–8 - PMC - PubMed
    1. Russell DW, and Wilson JD (1994) Steroid 5α-Reductase: Two genes/two enzymes. Annu. Rev. Biochem 63, 25–61 - PubMed

Publication types

MeSH terms

LinkOut - more resources