Extensive Challenges and Pending Advances in the Study of 5-Alpha-Reductase Isoenzymes: A Literature Review

August 2024 in “ Latin American Journal of Development ”

Iván Cortés-Pavía, Abel Moreno-Cárcamo, Abraham Landa-Piedra, Marisa Cabeza

5-alpha-reductase SRD5A androgenic alopecia SRD5A1 SRD5A2 SRD5A3 steroidal inhibitors non-steroidal inhibitors androgen-dependent disorders 5α-reductase androgenic hair loss

Studysummary In this review, the authors highlight the involvement of the 5α-reductase enzyme family in androgen-dependent disorders, noting the discovery of a novel isoform, SRD5A3, which is overexpressed in cancers with poor prognosis.

Our plain-language summary. Not medical advice or a treatment recommendation. Consult a qualified healthcare professional before changing treatment. Full disclaimer

This literature review examines the 5α-reductase enzyme family (SRD5A) and its involvement in androgen-dependent disorders, including androgenic alopecia. It highlights the discovery of a third isoform, SRD5A3, which is linked to poor prognosis in various cancers. The review notes the challenges in crystallizing these enzymes for structural analysis and mentions several effective inhibitors that have improved treatments for related conditions. While SRD5A1 and SRD5A2 are well-researched, the biochemical and physiological properties of SRD5A3 are not well understood, indicating a need for further study.

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Research cited in this study

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research Structure of Human Steroid 5α-Reductase 2 with the Anti-Androgen Drug Finasteride

30 citations , October 2020 in “Nature Communications”

This study provides the first crystal structure of the human SRD5A2 enzyme, revealing key insights into its function and inhibition which may aid future drug development.

research Subcellular Localization of the Five Members of the Human Steroid 5α-Reductase Family

13 citations , June 2017 in “Biochimie open”

This study determined that the human steroid 5α-reductase enzymes localize to the endoplasmic reticulum in HeLa cells, with protein tagging affecting expression and inducing protein aggregates for some isoforms.

research Discovery of a Novel Hybrid from Finasteride and Epristeride as 5α-Reductase Inhibitor

18 citations , October 2010 in “Bioorganic & Medicinal Chemistry Letters”

This study found that a new hybrid compound designed from finasteride and epristeride was a potent inhibitor of 5α-reductase with a mechanism similar to finasteride.

Human Type 3 5α-Reductase Is Expressed in Peripheral Tissues at Higher Levels Than Types 1 and 2 and Its Activity Is Potently Inhibited by Finasteride and Dutasteride

research Human Type 3 5α-Reductase Is Expressed in Peripheral Tissues at Higher Levels Than Types 1 and 2 and Its Activity Is Potently Inhibited by Finasteride and Dutasteride

45 citations , August 2010 in “Hormone Molecular Biology and Clinical Investigation”

This study found that SRD5a-3 is a highly efficient enzyme for converting hormones into androgens, with dutasteride being a much more potent inhibitor of SRD5a-3 than SRD5a-2.

research 5α-Reductase Isozymes and Androgen Actions in the Prostate

93 citations , February 2009 in “Annals of the New York Academy of Sciences”

This review describes the roles of 5α-reductase isozymes in prostate development and pathology and reports no new clinical results.

research Marked Suppression of Dihydrotestosterone in Men with Benign Prostatic Hyperplasia by Dutasteride, a Dual 5α-Reductase Inhibitor

408 citations , May 2004 in “The Journal of clinical endocrinology and metabolism/Journal of clinical endocrinology & metabolism”

This study found that dutasteride more effectively reduced serum dihydrotestosterone levels than finasteride in patients with benign prostatic hyperplasia.

research Selective Non-Steroidal Inhibitors of 5α-Reductase Type 1

49 citations , January 2004 in “Journal of steroid biochemistry and molecular biology/The Journal of steroid biochemistry and molecular biology”

This review discusses the development and selectivity of 5 alpha-reductase inhibitors, particularly non-steroidal ones, and reports no new clinical trial results.

research Effect of a Novel Steroid (PM-9) on the Inhibition of 5α-Reductase in Penicillium Crustosum Broths

22 citations , March 2003 in “Steroids”

This study found that both finasteride and a new steroidal compound, PM-9, competitively inhibit the 5α-reductase enzyme in Penicillium crustosum broth.

Cloning, Expression, and Characterization of Rhesus Macaque Types 1 and 2 5alpha-Reductase: Evidence for Mechanism-Based Inhibition by Finasteride

research Cloning, Expression, and Characterization of Rhesus Macaque Types 1 and 2 5alpha-Reductase: Evidence for Mechanism-Based Inhibition by Finasteride

25 citations , September 1998 in “The Journal of Steroid Biochemistry and Molecular Biology”

This study concludes that rhesus macaques are a suitable model for testing the pharmacological properties of finasteride and other 5aR inhibitors, due to their biochemical similarity to humans.

research The 5 Alpha-Reductase System and Its Inhibitors

124 citations , January 1996 in “Dermatology”

This article reviews the biochemical properties of 5 alpha-reductase isoforms and highlights the limited dermatological use of inhibitors like finasteride, especially for type 1 isozyme-targeting agents, while suggesting further clinical exploration.

research LY191704: A Selective, Nonsteroidal Inhibitor of Human Steroid 5 Alpha-Reductase Type 1

53 citations , June 1993 in “Proceedings of the National Academy of Sciences of the United States of America”

This study identified LY191704 as a specific noncompetitive inhibitor of human 5 alpha-reductase type 1, which may be useful in treating endocrine disorders related to DHT overproduction.

research Steroid 17β-Hydroxysteroid Dehydrogenase Deficiency in Man: An Inherited Form of Male Pseudohermaphroditism

46 citations , December 1992 in “The Journal of Steroid Biochemistry and Molecular Biology”

In this study, researchers observed that testicular 17β-hydroxysteroid dehydrogenase deficiency in an inbred Arab population in Israel leads to genital ambiguity at birth and progressive virilization after puberty.