Premium
Influences of Central Acting Drugs on Δ 4 ‐ ‐ 3‐Ketosteroid 5α‐Oxidoreductase Activity in Rat Diencephalon
Author(s) -
Kohsaka Mutsutoshi,
Kaneyulu Takao,
Shohmori Toshikiyo
Publication year - 1977
Publication title -
psychiatry and clinical neurosciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.609
H-Index - 74
eISSN - 1440-1819
pISSN - 1323-1316
DOI - 10.1111/j.1440-1819.1977.tb00137.x
Subject(s) - oxidoreductase , ketosteroid , chemistry , testosterone (patch) , endocrinology , medicine , diencephalon , enzyme , dihydrotestosterone , pharmacology , biochemistry , hormone , androgen , biology , central nervous system , isomerase
Summary Rat diencephalon homogenate was incubated with labeled testosterone in the presence of NADPH. The metabolic product was identified by GLC. TLC and estintation of constant specific activity. Testosterone is converted into dihydrotestosterone. The enzyme involved in this reaction is Δ 4 ‐ ‐ 3‐ketosteroid 5α‐oxidoreductase. The optimal pH of Δ 4 ‐ ‐ 3‐ketosteroid 5α‐oxidoreductase was 6.8 and the apparent Km value was 2.2 ± 10 ‐ ‐ 6 M. This enzyme showed the highest activity in the microsomal fraction, and it was inhibited up to 85.3 % by progesterone at a concentration of 1 ± 10 ‐ ‐ 5 M. The acute experimental group received a single intra peritoneal administration of diphenylhydantoin, imipramine or chlorpromazine. These animals were killed by decapitation four hours after drug administration. The chronic experimental group received an intra peritoneal administration of the same drugs for 14 consecutive days. These were sacrificed at 24 hours after the last injection. Immediately following decapitation the activity of rat diencephalon Δ 4 ‐ ‐ 3‐ketosteroid 5α‐oxidoreductase was estimated. The acute diphenylhydantoin group showed a significant increase of Δ 4 ‐ ‐ 3‐ketosteroid 5α‐oxidoreductase activity. All chronically treated animals showed a significant decrease in Δ 4 ‐ ‐ 3‐ketosteroid 5α‐oxidoreductase activity. The finding of central acting drugs altering Δ 4 ‐ ‐ 3‐ketosteroid 5α‐oxidoreductase activity suggests the possibility that testosterone and its metabolites may be involved in psychic state, either directly or indirectly.