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Steroidogenesis in Peripheral and Transition Zones of Human Prostate Cancer Tissue

The peripheral zone (PZ) and transition zone (TZ) represent about 70% of the human prostate gland with each zone having differential ability to develop prostate cancer. Androgens and their receptor are the primary driving cause of prostate cancer growth and eventually castration-resistant prostate c...

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Autores principales: Deb, Subrata, Chin, Mei Yieng, Pham, Steven, Adomat, Hans, Hurtado-Coll, Antonio, Gleave, Martin E., Tomlinson Guns, Emma S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825320/
https://www.ncbi.nlm.nih.gov/pubmed/33418978
http://dx.doi.org/10.3390/ijms22020487
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author Deb, Subrata
Chin, Mei Yieng
Pham, Steven
Adomat, Hans
Hurtado-Coll, Antonio
Gleave, Martin E.
Tomlinson Guns, Emma S.
author_facet Deb, Subrata
Chin, Mei Yieng
Pham, Steven
Adomat, Hans
Hurtado-Coll, Antonio
Gleave, Martin E.
Tomlinson Guns, Emma S.
author_sort Deb, Subrata
collection PubMed
description The peripheral zone (PZ) and transition zone (TZ) represent about 70% of the human prostate gland with each zone having differential ability to develop prostate cancer. Androgens and their receptor are the primary driving cause of prostate cancer growth and eventually castration-resistant prostate cancer (CRPC). De novo steroidogenesis has been identified as a key mechanism that develops during CRPC. Currently, there is very limited information available on human prostate tissue steroidogenesis. The purpose of the present study was to investigate steroid metabolism in human prostate cancer tissues with comparison between PZ and TZ. Human prostate cancer tumors were procured from the patients who underwent radical prostatectomy without any neoadjuvant therapy. Human prostate homogenates were used to quantify steroid levels intrinsically present in the tissues as well as formed after incubation with 2 µg/mL of 17-hydroxypregnenolone (17-OH-pregnenolone) or progesterone. A Waters Acquity ultraperformance liquid chromatography coupled to a Quattro Premier XE tandem quadrupole mass spectrometer using a C(18) column was used to measure thirteen steroids from the classical and backdoor steroidogenesis pathways. The intrinsic prostate tissue steroid levels were similar between PZ and TZ with dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT), pregnenolone and 17-OH-pregnenolone levels higher than the other steroids measured. Interestingly, 5-pregnan-3,20-dione, 5-pregnan-3-ol-20-one, and 5-pregnan-17-ol-3,20-dione formation was significantly higher in both the zones of prostate tissues, whereas, androstenedione, testosterone, DHT, and progesterone levels were significantly lower after 60 min incubation compared to the 0 min control incubations. The incubations with progesterone had a similar outcome with 5-pregnan-3,20-dione and 5-pregnan-3-ol-20-one levels were elevated and the levels of DHT were lower in both PZ and TZ tissues. The net changes in steroid formation after the incubation were more observable with 17-OH-pregnenolone than with progesterone. In our knowledge, this is the first report of comprehensive analyses of intrinsic prostate tissue steroids and precursor-driven steroid metabolism using a sensitive liquid chromatography-mass spectrometry assay. In summary, the PZ and TZ of human prostate exhibited similar steroidogenic ability with distinction in the manner each zone utilizes the steroid precursors to divert the activity towards backdoor pathway through a complex matrix of steroidogenic mechanisms.
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spelling pubmed-78253202021-01-24 Steroidogenesis in Peripheral and Transition Zones of Human Prostate Cancer Tissue Deb, Subrata Chin, Mei Yieng Pham, Steven Adomat, Hans Hurtado-Coll, Antonio Gleave, Martin E. Tomlinson Guns, Emma S. Int J Mol Sci Article The peripheral zone (PZ) and transition zone (TZ) represent about 70% of the human prostate gland with each zone having differential ability to develop prostate cancer. Androgens and their receptor are the primary driving cause of prostate cancer growth and eventually castration-resistant prostate cancer (CRPC). De novo steroidogenesis has been identified as a key mechanism that develops during CRPC. Currently, there is very limited information available on human prostate tissue steroidogenesis. The purpose of the present study was to investigate steroid metabolism in human prostate cancer tissues with comparison between PZ and TZ. Human prostate cancer tumors were procured from the patients who underwent radical prostatectomy without any neoadjuvant therapy. Human prostate homogenates were used to quantify steroid levels intrinsically present in the tissues as well as formed after incubation with 2 µg/mL of 17-hydroxypregnenolone (17-OH-pregnenolone) or progesterone. A Waters Acquity ultraperformance liquid chromatography coupled to a Quattro Premier XE tandem quadrupole mass spectrometer using a C(18) column was used to measure thirteen steroids from the classical and backdoor steroidogenesis pathways. The intrinsic prostate tissue steroid levels were similar between PZ and TZ with dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT), pregnenolone and 17-OH-pregnenolone levels higher than the other steroids measured. Interestingly, 5-pregnan-3,20-dione, 5-pregnan-3-ol-20-one, and 5-pregnan-17-ol-3,20-dione formation was significantly higher in both the zones of prostate tissues, whereas, androstenedione, testosterone, DHT, and progesterone levels were significantly lower after 60 min incubation compared to the 0 min control incubations. The incubations with progesterone had a similar outcome with 5-pregnan-3,20-dione and 5-pregnan-3-ol-20-one levels were elevated and the levels of DHT were lower in both PZ and TZ tissues. The net changes in steroid formation after the incubation were more observable with 17-OH-pregnenolone than with progesterone. In our knowledge, this is the first report of comprehensive analyses of intrinsic prostate tissue steroids and precursor-driven steroid metabolism using a sensitive liquid chromatography-mass spectrometry assay. In summary, the PZ and TZ of human prostate exhibited similar steroidogenic ability with distinction in the manner each zone utilizes the steroid precursors to divert the activity towards backdoor pathway through a complex matrix of steroidogenic mechanisms. MDPI 2021-01-06 /pmc/articles/PMC7825320/ /pubmed/33418978 http://dx.doi.org/10.3390/ijms22020487 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Deb, Subrata
Chin, Mei Yieng
Pham, Steven
Adomat, Hans
Hurtado-Coll, Antonio
Gleave, Martin E.
Tomlinson Guns, Emma S.
Steroidogenesis in Peripheral and Transition Zones of Human Prostate Cancer Tissue
title Steroidogenesis in Peripheral and Transition Zones of Human Prostate Cancer Tissue
title_full Steroidogenesis in Peripheral and Transition Zones of Human Prostate Cancer Tissue
title_fullStr Steroidogenesis in Peripheral and Transition Zones of Human Prostate Cancer Tissue
title_full_unstemmed Steroidogenesis in Peripheral and Transition Zones of Human Prostate Cancer Tissue
title_short Steroidogenesis in Peripheral and Transition Zones of Human Prostate Cancer Tissue
title_sort steroidogenesis in peripheral and transition zones of human prostate cancer tissue
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825320/
https://www.ncbi.nlm.nih.gov/pubmed/33418978
http://dx.doi.org/10.3390/ijms22020487
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