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5α-Reductases in Human Physiology: An Unfolding Story.
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5α-Reductases in Human Physiology: An Unfolding Story.
Endocr Pract. 2012 Jul 11:1-38. [Epub ahead of print]
5α-Reductases in Human Physiology: An Unfolding Story.
Traish AM.
Department of Urology, Boston University School of Medicine, Boston, Massachusetts, USA.
Objective: 5α-reductases are a family of isozymes expressed in a wide host of tissues including the central nervous system and play a pivotal role in male sexual differentiation, development and physiology.Methods: A comprehensive literature search from 1970-2011 was made via PubMed and the relevant information was summarized.Results: 5α reductases convert testosterone, progesterone, deoxycorticosterone, aldosterone and corticosterone into their respective 5α -dihydro-derivatives, which serve as substrates for 3α - hydroxysteroid dehydrogenase (3α-HSD) enzymes. The latter transforms these 5α-reduced metabolites into a subclass of neuro-active steroid hormones with distinct physiological function. The neuro-active steroid hormones modulate multitude of functions in human physiology encompassing regulation of sexual differentiation, neuro-protection, memory enhancement, anxiety, sleep and stress, among others. In addition, 5α -reductase type 3 is also implicated in the N-glycosylation of proteins via formation of dolichol phosphate. The family of 5α-reductases was targeted for drug development to treat pathophysiological conditions, such as benign prostatic hyperplasia (BPH) and androgenetic alopecia (AGA). While the clinical use of 5α-reductases inhibitors was well established, the scope and the magnitude of the adverse side effects of such drugs especially on the central nervous systems is still unrecognized, due to lack of knowledge of the various physiological function of this family of enzymes, especially in the central nervous system.Conclusion: There is an urgent need to better understand the function of 5α-reductases and the role of neuro-active steroids in human physiology in order to minimize the potential adverse side effects of inhibitors targeting 5α-reductases to treat BPH and AGA.
5α-Reductases in Human Physiology: An Unfolding Story.
Traish AM.
Department of Urology, Boston University School of Medicine, Boston, Massachusetts, USA.
Objective: 5α-reductases are a family of isozymes expressed in a wide host of tissues including the central nervous system and play a pivotal role in male sexual differentiation, development and physiology.Methods: A comprehensive literature search from 1970-2011 was made via PubMed and the relevant information was summarized.Results: 5α reductases convert testosterone, progesterone, deoxycorticosterone, aldosterone and corticosterone into their respective 5α -dihydro-derivatives, which serve as substrates for 3α - hydroxysteroid dehydrogenase (3α-HSD) enzymes. The latter transforms these 5α-reduced metabolites into a subclass of neuro-active steroid hormones with distinct physiological function. The neuro-active steroid hormones modulate multitude of functions in human physiology encompassing regulation of sexual differentiation, neuro-protection, memory enhancement, anxiety, sleep and stress, among others. In addition, 5α -reductase type 3 is also implicated in the N-glycosylation of proteins via formation of dolichol phosphate. The family of 5α-reductases was targeted for drug development to treat pathophysiological conditions, such as benign prostatic hyperplasia (BPH) and androgenetic alopecia (AGA). While the clinical use of 5α-reductases inhibitors was well established, the scope and the magnitude of the adverse side effects of such drugs especially on the central nervous systems is still unrecognized, due to lack of knowledge of the various physiological function of this family of enzymes, especially in the central nervous system.Conclusion: There is an urgent need to better understand the function of 5α-reductases and the role of neuro-active steroids in human physiology in order to minimize the potential adverse side effects of inhibitors targeting 5α-reductases to treat BPH and AGA.
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TrueGround- Posts : 208
Join date : 2012-01-05
Re: 5α-Reductases in Human Physiology: An Unfolding Story.
5a-reductase .. the neverending story, lol.
Amaranthaceae- Posts : 1368
Join date : 2008-07-15
Location : Copenhagen
Re: 5α-Reductases in Human Physiology: An Unfolding Story.
Not to mention 3b-adiol.
baller234- Posts : 433
Join date : 2010-02-12
Age : 35
Re: 5α-Reductases in Human Physiology: An Unfolding Story.
Baller,
I'm very new to the pro-hormone world, so correct me if I'm wrong, but isn't that epistane? My younger brother is using it as an aromatase inhibitor and loves it. Can't imagine its wonderful for the liver.
CS,
Good post. Highlights the narrow minded paradigms prevalent in the medical world. Oh this enzyme catalyzes this one reaction, well we'd better inhibit it. Who cares about all of its other physiological functions? We'll burn that bridge when we come to it.
I'm very new to the pro-hormone world, so correct me if I'm wrong, but isn't that epistane? My younger brother is using it as an aromatase inhibitor and loves it. Can't imagine its wonderful for the liver.
CS,
Good post. Highlights the narrow minded paradigms prevalent in the medical world. Oh this enzyme catalyzes this one reaction, well we'd better inhibit it. Who cares about all of its other physiological functions? We'll burn that bridge when we come to it.
AS54- Posts : 2367
Join date : 2011-08-12
Age : 35
Location : MI
Re: 5α-Reductases in Human Physiology: An Unfolding Story.
No I don't believe so. 3b-adiol is metabolized from DHT by 3b-HSD and 17b-HSD. It's an anti carcinogenic androgen that binds to estrogen receptor beta. Really quite interesting and something that finasteride completely shuts down.
http://www.townsendletter.com/July2012/anticancer0712.html
http://www.townsendletter.com/July2012/anticancer0712.html
baller234- Posts : 433
Join date : 2010-02-12
Age : 35
Re: 5α-Reductases in Human Physiology: An Unfolding Story.
Haha. First of all, I stated the wrong name. The product he is using is called arimistane, not epistane. And its chemical name is different.
AS54- Posts : 2367
Join date : 2011-08-12
Age : 35
Location : MI
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