Testosterone-5a-reductase

Enzyme kinetic studies of inhibitor are very important for considering as a therapeutic agent. It is interesting to note that isoprenoid-substituted flavonoids having non-steroidal structures are potent un-competitive inhibitors of 5a-reductase. So, it would be expected that the isoprenoid-substituted flavonoid derivative would be an interesting lead compounds for testosterone 5a-reductase inhibitor. 

Table 11. Effects of Moras flavonoids on testosterone 5a-reductase...

Takamatsu S, Rho M-C, Masuma R, Hayashi M, Komiyama K, Tanaka H, Omura S (1994) A Novel Testosterone 5a-Reductase Inhibitor, 8 ,9 -Dehydroascochlorin Produced by Verticillium sp. FO-2787. Chem Pharm Bull 42 953... 

R, R group of amino acid 5aR, testosterone 5a-reductase cr-R, sigma receptor (metabotropic or ionotropic)... 

Endothelium-dependent pulmonary artery contractions in response to arachidonic acid or methacholine appeared to be mediated by TXAj in rabbits (179). However, approximately 25% of normal New Zealand White rabbits ftuled to demonstrate pulmonary artery contraction in response to arachidonic acid, U46619 or I-BOP. These "unresponsive" rabbits were found to have only 23% of the TP receptors present on pulmonary and aortic crade membranes of "responsive" rabbits (179). Of interest was the feet that platelets fix>m "unresponsive" rabbits aggregated as well or better than platelets firom "responsive" animals vdien stirred with U46619, and no deficiency ofTP receptors nor binding affinity was found. These data sug sted that TP receptor expression may be tissue tecific. This conclusion was supported by the observation that ir bition of testosterone 5a-reductase in tats decreased TP receptor density on aortic membranes but not on platelets (180) (See V. ALTERED TP RECEPTOR FUNCTION, 3. DRUG EFFECTS, a. HORMONES below). 

Higashiura K, Blaney B, Morgan E, Madmr RS, Haluddca PV. Inhilrition of testosterone 5a-reductase evidence for tissue-spedficregidationofdiromboxaneAj receptors JPharmacol Exp Hier 1996 279 1386-91... 

Niederprum, H., Schweikert, H. and Zanker, K. 1994, Testosterone 5a-reductase inhibition by free fatty acids from Sabal serrulata fruits . Phytomedicine 1 127-133. 

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