Molecular interactions of Levonorgestrel and its 5α-reduced derivative with androgen receptors in hamster flanking organs

Evaluation of New Pregnane Derivatives as 5.ALPHA.-Reductase Inhibitor.

“…8,9) The inhibitory effect of finasteride in flank organs was previously demonstrated. 10) Table 1 shows the percentages of [1,2-14 C]sodium acetate incorporation into lipids as well as the rate of this incorporation.…”

“…8) Table 1 demonstrates very clearly that finasteride as well as steroids 7, 8, 13, 16-19 decreased the rate and the percentage of radiolabeled sodium acetate incorporation expressed as nmol/gland. These results show that the above mentioned steroids are strong inhibitors of the incorporation of sodium acetate into lipids in the sebaceous glands and consequently are antiandrogens.…”

“…2, 3) was determined in vitro following the transformation of T (1) to DHT (2) produced by 5a-reductase enzyme in Penicillium crustosum broth, 13,14) by the in vivo steroid action upon the flank organs where the DHT is bound to its cognate receptor, 15,16) and also by the incorporation of radiolabeled sodium acetate into lipids in these glands. 8,9) Effect of the Synthesized Steroids on the Conversion of T to DHT in P. crustosum Conversion of T (1) to DHT (2) has been demonstrated in P. decumbens and P. crustosum broth obtained from fermented pistachios, lemons and corn tortillas. 13,14) In this experiment, when extracts from P. crustosum were spotted onto TLC plates, the Rf value (0.33) of the zone corresponding to 5a-DHT standard was determined.…”

“…Radiolabeled T in the incubated medium increases significantly its conversion to DHT compared to T plus finasteride (3 Flank Organ Test To test the effect of the synthesized compounds as 5a-reductase inhibitors, we used the flank organs of gonadectomized male hamsters. 8,16) Hamster flank organs are dorsal spots on the skin that are composed of pilosebaceous tissue. These glands are androgen dependent tissue that decreases upon castration and increase in diameter size with daily injections of T. The flank organs can convert T to DHT and are used for the screening of new antiandrogenic drugs.…”

“…The counting solution efficiency for 14 C was 87%. The specific activity of the incorporated radiolabeled sodium acetate in lipids was calculated and expressed as nmol/gland/h 8,9) and as a percentage of incorporation of the total radioactivity used. The results were analyzed using one-way Anova with Epistat software.…”