in vitro models to test 5a-Reductase Inhibition (prostata) 

Biochemistry

5a reductase (3-oxo-5a-steroid-D4-dehydrogenase; 5aR), a NADPH-dependent membrane protein, irreversibly catalyses the reduction of 4-en-3-oxosteroids, resulting in the corresponding 5a-3-oxosteroids. The most important reaction is the conversion of testosterone (T) to the most potentandrogen 5a-dihydrotestosterone (DHT), which displays the highest affinity towards the androgen receptor. The irreversible reduction of T to DHT represents the final step in androgen biosynthesis. In humans, two 5a reductase isoenyzme are expressed: 5a reductase type I and 5a reductase type II. The isoenzymes have a different distribution pattern, which is still under discussion. In principle, type I is predominantly expressed in skin, scalp and follicles, whereas type II is mainly found in prostate tissue. However, more recent reports describe that 5a reductase I is the predominant form in oil and sweat glands. In stroma and basal cells of the prostate, 5a reductase type II is expressed, but Shirakawa et al. (2004) demonstrated that in epithelial cells of the prostate, also 5a reductase I is expressed. 5a-reductase type I and type II display distinct biochemical and pharmacological properties, such as pH-optimum, Km etc.

Pathophysiology

Elevated DHT levels correlate with the pathogenesis and progression of androgen-dependent diseases such as prostate cancer (PCa) and benign prostatic hyperplasia (BPH), which is the most common benign tumor affecting over 50% of men above the age of 70. Both conditions have been successfully treated with drugs that lower the level of DHT available to prostate tissue, so-called 5a reductase inhibitors, blocking the action of the enzyme 5a reductase that converts T into DHT.

At VivaCell, we offer to test compounds or extracts for in vitro 5a-Reductase Inhibition (Type I and Type II)

Literature:

Shirakawa T.; Okada H.; Acharya B.; Zhang Z.; Hinata N. et al. Messenger RNA levels and enzyme activities of 5 alpha-reductase types 1 and 2 in human benign prostatic hyperplasia (BPH) tissue. Prostate 2004, 58, 33-40.