5α-Reductase, an enzyme regulating glucocorticoid action in the testis of Rhinella arenarum (Amphibia: Anura).

摘要: The reduction of A-ring glucocorticoids to produce 5α-dihydro-derivatives by 5α-reductases has been considered as a pathway irreversible inactivation. However, 5α-reduced metabolites corticosterone and testosterone have significant biological activity. In this paper, we investigated whether toad testicular 5α-reductase (5α-Red) is able transform into 5α-dihydrocorticosterone. Furthermore, studied the role metabolite glucocorticoid receptor (GR) agonist. activity 5α-Red was assayed in subcellular fractions with [(3)H]corticosterone or [(3)H]testosterone substrate. enzyme localizes microsomes its optimal pH between 7 8. not inhibited finasteride. These results support conclusion that resembles mammalian type 1 isoenzyme. Kinetic studies indicate neither K(m) nor V(max) for both were significantly different among reproductive periods. value higher than corticosterone, indicating C-21 steroid preferred substrate enzyme. Studies binding capacity 5α-dihydrocorticosterone (5α-DHB) GR show 5α-DHB displace [(3)H]dexamethasone cytosol similar potency corticosterone. inhibition constant (Ki) values similar, 31.33±2.9 nM 35.24±2.3 nM, respectively. vitro experiments suggest an agonist GR, decreasing key androgen synthesis, cytochrome P450 17-hydroxylase, C17,20-lyase.