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Your search keyword '"Androstenedione"' showing total 2 results
2 results on '"Androstenedione"'

1. Characterization of equine GST A3-3 as a steroid isomerase.

Author

Lindström, Helena, Mannervik, Bengt, Peer, Shawna M., and Ing, Nancy H.

Subjects
*STEROIDS, *ISOMERASES, *PROGESTERONE, *TESTOSTERONE, *ISOMERIZATION
Abstract

Glutathione transferases (GSTs) comprise a superfamily of enzymes prominently involved in detoxication by making toxic electrophiles more polar and therefore more easily excretable. However some GSTs have developed alternative functions. Thus, a member of the Alpha class GSTs in pig and human tissues is involved in steroid hormone biosynthesis, catalyzing the obligatory double-bond isomerization of Δ 5 -androstene-3,17-dione to Δ 4 -androstene-3,17-dione and of Δ 5 -pregnene-3,20-dione to Δ 4 -pregnene-3,20-dione on the biosynthetic pathways to testosterone and progesterone. The human GST A3-3 is the most efficient steroid double-bond isomerase known so far in mammals. The current work extends discoveries of GST enzymes that act in the steroidogenic pathways in large mammals. The mRNA encoding the steroid isomerase GST A3-3 was cloned from testis of the horse ( Equus ferus caballus). The concentrations of GSTA3 mRNA were highest in hormone-producing organs such as ovary, testis and adrenal gland. EcaGST A3-3 produced in E. coli has been characterized and shown to have highly efficient steroid double-bond isomerase activity, exceeding its activities with conventional GST substrates. The enzyme now ranks as one of the most efficient steroid isomerases known in mammals and approaches the activity of the bacterial ketosteroid isomerase, one of the most efficient enzymes of all categories known today. The high efficiency and the tissue distribution of EcaGST A3-3 support the view that the enzyme plays a physiologically significant role in the biosynthesis of steroid hormones. [ABSTRACT FROM AUTHOR]

Published
2018
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2. Steroidogenesis in Peripheral and Transition Zones of Human Prostate Cancer Tissue

Author

Emma S. Tomlinson Guns, Martin E. Gleave, Mei Yieng Chin, Hans Adomat, Antonio Hurtado-Coll, Steven Pham, and Subrata Deb

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
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, 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.

Published
2021

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