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Steroidogenesis in Peripheral and Transition Zones of Human Prostate Cancer Tissue
- Source :
- International Journal of Molecular Sciences, Vol 22, Iss 487, p 487 (2021), International Journal of Molecular Sciences, Volume 22, Issue 2
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- 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 &micro<br />g/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 C18 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.
- Subjects :
- Male
0301 basic medicine
steroidogenesis
medicine.medical_treatment
Mass Spectrometry
lcsh:Chemistry
Prostate cancer
0302 clinical medicine
Prostate
Testosterone
backdoor pathway
classical pathway
lcsh:QH301-705.5
Chromatography, High Pressure Liquid
Progesterone
Spectroscopy
Chemistry
General Medicine
prostate cancer
Computer Science Applications
medicine.anatomical_structure
030220 oncology & carcinogenesis
Dihydrotestosterone
prostate tissue metabolism
Pregnenolone
Steroids
medicine.drug
medicine.medical_specialty
Dehydroepiandrosterone
Androsterone
Article
Catalysis
Steroid
Inorganic Chemistry
03 medical and health sciences
Internal medicine
medicine
Humans
Physical and Theoretical Chemistry
Molecular Biology
liquid chromatography-mass spectrometry
Organic Chemistry
Androstenedione
Prostatic Neoplasms
Cancer
medicine.disease
030104 developmental biology
Endocrinology
lcsh:Biology (General)
lcsh:QD1-999
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....eaede3033a6ad23f4e03975e5b3dd759