In vivo and in vitro effect of androstene derivatives as 5α-reductase type 1 enzyme inhibitors

Figures & data

Table 1.  Effect of the testosterone concentration on 5α-reductase type 1 activity at different pHs. Solubilized microsomes from rat liver were used as source of 5α-reductase type 1.

	Concentration nM								5α-Reductase type 1 efficiency	Vmax pmol/mL/h	Km [µM]
T	38.2	96.4	196	500	1250	1670	2300	4000
pH 6.5% of Conversion to DHT	1.87	2.37	2.44	2.86	2.28	2.91	1.53	1.33
pmol/mL/h	0.71	2.29	4.68	14.3	28.5	48.59	33.19	53.2	37.03	100	2.97
T	500	1250	1670	2300	4000	5180	6100	6308
pH 7.5% of Conversion to DHT	4.01	3.32	3.88	4.1	3.5	3.66	3.75	3.48
pmol/mL/h	20.05	41.5	64.79	94.3	140	189.5	200	219.5	40.16	1111.1	27.6
pH 8% of Conversion to DHT	0.667	2.33	1.17	2.04	1.94	1.83	1.89	2.80
pmol/mL/h	3.33	29.13	19.53	46.92	77.6	94.79	125.2	176.62	18.78	526	28

Figure 1.  Steroidal structures and effect of different dehydroepiandrosterone derivatives on the activity of 5α-R enzyme type 1 and 2 (5α-R): 1–12. The IC₅₀ values indicate the required concentration of the novel steroids for the inhibition of 50% of the activity of 5α-R1 and 5α-R2. This figure shows also the relative binding affinity (RBA) of these derivatives to the androgen receptor (AR). The following abbreviations were used: NA, non active compound.

Figure 2.  Diameter size ± standard deviations of the pigmented spot from gonadectomized hamster’s flank organs receiving different treatments with T plus the novel steroids for 6 days. Control gonadectomized hamsters were treated with vehicle only. The following abbreviations were used: Testosterone (T), Finasteride (F). *Significant differences with the T-treatment were observed.