[Lotus]

Milk Thistle inhibits testosterone:


Time- and Concentration-Dependent Inactivation of Testosterone Metabolism of P450 3A4 by Silybin. 6 -Hydroxytestosterone was the major metabolite detected when testosterone was incubated with purified recombinant P450 3A4 in a reconstituted system in the presence of NADPH. Silybin inhibited the metabolism of testosterone by P450 3A4 in a time-, concentration-, and NADPH-dependent manner.   

SILYBIN INACTIVATES CYTOCHROMES P450 3A4 AND 2C9 AND INHIBITS MAJOR HEPATIC GLUCURONOSYLTRANSFERASES 
http://dmd.aspetjournals.org/content/dmd...7.full.pdf

From the study, approximately 250mg of SILYBIN (milk thistle) was used to inhibit Testosterone, and metabolized in about 9 to 18 min. Here's the real find though:

silybin (milk thistle) inhibits both phase I and phase II enzymes which inactivates P450s 3A4. Additionally, Silybin was approximately 14- and 20-fold more selective at inhibiting UGT1A1 (aka-Glucuronidation) which is an important metabolic pathway in the liver such as steroid hormones.

Now, from my calculations using pseudofirst-order kinetics, milk thistle decreases T approximately 62% in 9-18min.....or, I could be way off on this one. 

Time- and Concentration-Dependent Inactivation of the 7EFC Activity of P450 2C9. As shown in Fig. 4, with P450 2C9 the silybin-mediated inactivation of the 7EFC O-deethylation activity was also time-, concentration-, and NADPH-dependent. Approximately 35% activity loss was seen in 15 min when 50 M silybin was used. The inactivation exhibited pseudofirst-order kinetics. The double- reciprocal plot of the values of the initial rate constants versus the silybin concentrations gave a KI of 5 M, a kinact of 0.14 min 1, and t1/2 of 7 min. 

Transcriptional regulation of human UDP-glucuronosyltransferase genes.
Hu DG1, Meech R, McKinnon RA, Mackenzie PI.
Author information


Abstract
Glucuronidation is an important metabolic pathway for many small endogenous and exogenous lipophilic compounds, including bilirubin, steroid hormones, bile acids, carcinogens and therapeutic drugs. Glucuronidation is primarily catalyzed by the UDP-glucuronosyltransferase (UGT) 1A and two subfamilies, including nine functional UGT1A enzymes (1A1, 1A3-1A10) and 10 functional UGT2 enzymes (2A1, 2A2, 2A3, 2B4, 2B7, 2B10, 2B11, 2B15, 2B17 and 2B28). Most UGTs are expressed in the liver and this expression relates to the major role of hepatic glucuronidation in systemic clearance of toxic lipophilic compounds. Hepatic glucuronidation activity protects the body from chemical insults and governs the therapeutic efficacy of drugs that are inactivated by UGTs. UGT mRNAs have also been detected in over 20 extrahepatic tissues with a unique complement of UGT mRNAs seen in almost every tissue. This extrahepatic glucuronidation activity helps to maintain homeostasis and hence regulates biological activity of endogenous molecules that are primarily inactivated by UGTs. Deciphering the molecular mechanisms underlying tissue-specific UGT expression has been the subject of a large number of studies over the last two decades. These studies have shown that the constitutive and inducible expression of UGTs is primarily regulated by tissue-specific and ligand-activated transcription factors (TFs) via their binding to cis-regulatory elements (CREs) in UGT promoters and enhancers. This review first briefly summarizes published UGT gene transcriptional studies and the experimental models and tools utilized in these studies, and then describes in detail the TFs and their respective CREs that have been identified in the promoters and/or enhancers of individual UGT genes.