5-a-reductase

Spironolactone is an antiandrogen which blocks androgen-receptors, alters steroidogenesis by adrenals and gonads and inhibits 5-a reductase. In doses of 100-200 mg daily it reduces sebum production and improves inflammatory acne in women. During treatment, birth control measures are required due to the risk of male fetus feminization. 

Hormonal Does not occur in eunuchs. Low incidence in cirrhotic patients. Up to 80% are hormonally dependent. African-Americans have 15% increased testosterone. Japanese have decreased 5-a-reductase activities. Polymorphic expression of the androgen receptor. 

Cyproterone acetate6 Progesterones 5-a-reductase inhibition Finasteride6... 

Antiandrogens inhibit the formation of the DHT-receptor complex and thereby interfere with androgen-mediated action at the cellular level.22 Megestrol acetate, a progestational agent, also is available and has antiandrogen actions.21 Finally, the conversion of testosterone to DHT may be inhibited by 5-a-reductase inhibitors.6... 

Only 2% of total plasma testosterone is present in the active unbound state that penetrates the prostate cell, where it is converted to DHT by 5 a-reductase. DHT subsequently binds with a cytoplasmic receptor and is transported to the cell nucleus where transcription and translation of stored genetic material occur. 

Saw palmetto extract can inhibit the enzyme 5-a-reductase in vitro. This enzyme converts testosterone into dihydrotestosterone (DHT), which in turn contributes to prostatic enlargement. Saw palmetto also appears to have an antiinflammatory effect and can reduce DHT binding to prostatic androgen receptors (antiandrogenic effect). Despite its proposed 5-a-reductase mechanism. 

The biological activity of isoprenylated chalcones from the Moraceae has been described both in original papers and reviews. Of particular interest is the potent 5-a-reductase inhibition shown by a geranylated chalcone (84) isolated from leaves of Artocarpus incisus The inhibitory effect is decreased by a factor of 2 when the geranyl substituent is lacking, as in butein (2, 4, 3,4-tetrahydroxychalcone). Compound 41, which was obtained from the leaves of Madura tinctoria together with four known isoprenylated flavonoids, showed inhibitory... 

The scheme used to produce a somewhat more complex 5-a-reductase inhibitor relies on a chiral auxiliary to yield the final product as a single enantiomer. The first step in a sequence similar to that above starts with the reaction of bromotetralone (23-1) with R-a-phenethyl amine (23-2) to afford the enamine (23-3). Reaction with methyl iodide adds the methyl group at what will be a steroid-like AB ring junction... 

The management of lower urinary tract symptoms suggestive of clinical symptomatic BPH remains somewhat controversial. Treatment options range from watchful waiting, for those patients wishing to delay any active therapy, to minimally invasive treatment, such as transurethral needle ablation of the prostate and transurethral microwave therapy, to surgical interventions in the form of transurethral prostatectomy or open enucleation of the prostate. Most patients present with difficulties in urination for which a variety of medical therapies are available, including synthetic 5-a-reductase inhibitors, a-blockers, and plant extracts (Boyle et al., 2000). 

All classes of steroid hormones bind to specific cytoplasmic receptors in their respective target tissues, and are then translocated to the nucleus. For example, testosterone, a lipid-soluble substance, enters the cell and is enzymatically reduced to dihydrotestosterone by 5-a reductase. Dihydrotestosterone then becomes bound to a specific androgen receptor site located in the cytoplasm. This complex becomes activated and is then translocated to the nucleus, where it binds to the chromatin acceptor site consisting of DNA and nonhistone chromosomal proteins. This interaction results in the transcription of a specific messenger RNA that is then relocated to the cytoplasm and translated on the cytoplasmic ribosomes, resulting in the synthesis of a new protein that sponsors the androgenic functions (Figure 61.6). 

Propecia Finasteride 1 mg Tablet Male pattern hair loss A specific inhibitor of steroid type II 5 a-reductase Lactose monohydrate, MCC, pregelatinized starch, sodium starch glycolate, docusate sodium, magnesium stearate, Hypromellose 2910 Merck Co. 

Inhibition of 5-a-Reductase by 17/3-(JV-(X-phenyl)carbamoyl)-6-azaan-drost-4-ene-3-ones, II, 36... 

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