Research articals

[Young JD]

*

Steroids
Volume 54, Issue 3, September 1989, Pages 299-311
doi:10.1016/0039-128X(89)90004-4*|*How to Cite or Link Using DOI
Cited By in Scopus (8)
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3β-hydroxyandrost-4-en-6-one derivatives as aromatase inhibitors
Mitsuteru*Numazawa*, Ayako*Mutsumi, Masachika*Tsuji


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Tohoku College of Pharmacy, 4-1 Komatsushima-4-chome, Sendai 981, Japan
Received 29 September 1988; revised 27 January 1989; Available online 27 April 2004.

Abstract
The 3-formate (II), 3-acetate (III), 3-bromoacetate (IV), 3-propionate (V), 3-methyl ether (VI), and 3-deoxy-derivative (VII) of 3β-hydroxyandrost-4-ene-6,17-dione (I) were synthesized and tested in human placental microsomes for their ability to inhibit aromatase. II, III, and VII of this series were potent inhibitors of aromatase with the IC50's (1.7 and 3.3 μM) of the latter two comparable to that (1.2 μM) of 4-hydroxyandrostenedione. Kinetic studies showed that the three steroids are competitive inhibitors of the enzyme with Ki's of 16.0, 5.5, and 0.61 μM for II, III, and VII. Furthermore, II showed a time-dependent, pseudo-first order rate of inactivation of aromatase with Ki of 20.5 μM and kinact of 1.54 × 10−2 min−1, while III gave a time-dependent, biphasic loss of the enzyme activity. NADPH and oxygen were required for the time-dependent inactivation and the substrate, androstenedione, prevented it.


Corresponding author: Mitsuteru Numazawa




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Copyright © 1989 Published by Elsevier Inc.
Steroids
Volume 54, Issue 3, September 1989, Pages 299-311

 

[Young JD]

Steroids
Volume 67, Issue 12, November 2002, Pages 953-966
Steroids Signalling: New Frontiers
doi:10.1016/S0039-128X(02)00043-0*|*How to Cite or Link Using DOI
Cited By in Scopus (44)
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Immune up-regulation and tumor apoptosis by androstene steroids
In memoriam: A colleague and friend, Dr. Osamu Nishikaze, recently passed away. Dr. Nishikaze, carried out pioneering work on the metabolism of urinary keto steroids in stress and disease. In 1996, the Emperor of Japan recognized Dr. Nishikaze for his scientific work and appointed him to the Imperial order. His inquiring mind and vivid spirit will be missed.
Roger M*Loria*,*


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Department of Microbiology, Immunology and Pathology, Medical College of Virginia, Virginia Commonwealth University, 1101 East Marshal Street, Richmond, VA 23298-0768, USA
Available online 17 September 2002.

Abstract
β Androstenes steroid up-regulates immunity to increase resistance against lethal infection and lethal radiation, and mediates a rapid recovery of hematopoietic precursor cells after radiation injury. β Androstenetriol increases the levels of the TH1 cytokines, IL-2, IL-3, IFNγ and counteracts hydrocortisone mediated immune suppression. In contrast, 17α androstenediol inhibits proliferation and mediates apoptosis in tumor cells of murine and human origin. Its epimer 17β androstenediol does not. The antiproliferative functions of 17α androstenediol are not dependent on either the estrogen or androgen receptors.

Our findings show that β androstenes and analogs protect the host from lethal infection by DNA or RNA viruses such as, herpesvirus type 2, coxsackievirus B4, influenza, and arthropod borne viruses. These androstenes also protected the host from lethal bacterial infections by Enterococcus faecalis, Pseudomonas aeruginosa, and Klebsiella pneumonia and from parasites infections, i.e. Cryptosporidium parvum, and malaria.

In vivo, the level of potency follows the order: with the latter being up to one hundred thousand times more potent in protecting the host from infections than the first. In vitro, their effects are also dramatically different from one another with only β androstenetriol potentiating the cellular response by increasing lymphocyte activation and counteracting hydrocortisone immune-suppressive activity. Conceptually, the androstenes form a new and different subclass of steroid hormones with unique physiological properties. Following host injury, the balance between the epimers and isomers is a determining factor in the overall regulation of hematopoiesis, THl/TH2 balance, and host resistance to infections and tumor growth.

Keywords: Steroids; Immune regulation; Apoptosis; Androstenetriol; Androstenediol

Article Outline
1. Introduction
2. Results
2.1. Immune up-regulation by dehydroepiandrosterone
2.2. Immune up-regulation by androstenediol
2.3. In vitro studies
2.4. Radiation studies
2.5. 17α Androstenediol apoptosis
3. Discussion
Acknowledgements
References

Tel.: +1-804-828-9717; fax: +1-804-828-5862.




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Copyright © 2002 Elsevier Science Inc. All rights reserved.
Steroids
Volume 67, Issue 12, November 2002, Pages 953-966
Steroids Signalling: New Frontiers

 

[Young JD]

Steroids
Volume 30, Issue 1, July 1977, Pages 15-23
doi:10.1016/0039-128X(77)90132-5*|*How to Cite or Link Using DOI
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Androgen receptor protein binding properties and tissue distribution of 2-selena-a-nor-5α-androstan-17β-ol in the rat
R.W.Scot*Skinner, Rodney V.*Pozderac*, Raymond E.*Counsell, Chen-Fu*Hsu, Paul A.*Weinhold


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Nuclear Medicine Service and the Biochemical Research Service (7169:02), Veterans Administration Hospital and the Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan, USA
Received 21 May 1977; Available online 16 January 2003.

Abstract
2-selena-A-nor-5α-androstan-17β-ol was studied and in the rat prostate gland. The data demonstrates the ability of this compound to selectively complex with the specific receptors of 5α-dihydrotestosfcerone (5α-DHT) in the cytosol and to be retained in the nuclei in an unaltered form. Studies with selenium-75 labeled material suggests that the uptake and localization is similar to endogenous 5α-dihydrotestosterone.


Reprint requests should be submitted to R. V. Pozderac, M. D., VA Hospital, 2215 Fuller Road, Ann Arbor, Michigan 48105.




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Copyright © 1977 Published by Elsevier Inc.
Steroids
Volume 30, Issue 1, July 1977, Pages 15-23
A intersting articale