RESUMEN
The NADPH-dependent reduction activities of two paralogous pig AKR1C1s with and without 19 additional amino acid residues in C-terminus were evaluated against steroid hormones including 5a-dihydrotestosterone, testosterone, progesterone, androstenedione and 5a-androstane-3,17-dione, which act as substrates of the AKR1C1s. Among the hormones, the AKR1C1s exhibited the highest activity against 5a-dihydrotestosterone and the lowest activity against testosterone and progesterone. Furthermore, the AKR1C1s showed the largest differential activities against 5a-dihydrotestosterone, but no such change of activities was found against progestrone and testosterone. These results suggest that the C-terminal region of AKR1C1 plays an important effect in the reduction activities of pig AKR1C1. Thus, the differential activities of two AKR1C1 paralogs observed in the present study provide important insights in understanding the molecular evolution.
Asunto(s)
20-Hidroxiesteroide Deshidrogenasas/química , Animales , Activación Enzimática , Hormonas Esteroides Gonadales/química , NADP/química , Oxidación-Reducción , Relación Estructura-Actividad , PorcinosRESUMEN
The activities of L-tryptophan 2, 3-dioxygenase [EC 1. 13. 11. 11], pyridoxal phosphokinase [EC 2. 7. 1. 35], kynurenine transaminase [EC 2. 6. 17] and kynurenine hydrolase [EC 3. 7. 1. 2] were determined in female rats, following two weeks of sex steroid administration, to assess their effect on tryptophan metabolism. Steroid effect is also studied on carbohydrate metabolism, through an evaluation of blood glucose, liver glycogen and serum cortisol levels. Administration of testosterone propionate [TP] and combination of ethinyl estradiol plus progesterone [EE+P], resulted in a significant decrease in the activity of L-tryptophan 2, 3-dioxygenase. Pyridoxal phosphokinase was significantly inhibited by [TP], while [EE+P] caused a significant increase in its activity, [TP] and [EE+P] produced an inhibitory effect on kynurenine transaminase and kynurenine hydrolase. Liver glycogen content was significantly increased by [TP] and [EE+P], while blood glucose level and serum cortisol concentration were not changed significantly. In conclusion, male and female hormones produce a disorder in tryptophan metabolism. Some abnormalities in carbohydrate metabolism are also observed