Different mechanisms of regulation of nuclear reduced nicotinamide adenine dinucleotide phosphate dependent 3 oxo steroid 5α reductase activity in rat liver, kidney and prostate

J. A. Gustafsson, A. Pousette

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The regulatory mechanisms involved in the control of the nuclear NADPH dependent 3 ketosteroid 5α reductase (5α reductase) activity were studied in liver, kidney and prostate. The substrate used was [1,2 3H] androst 4 ene 3,17 dione (androstenedione) (for liver and kidney) or [4 14C] androstenedione (for prostate). The hepatic nuclear 5α reductase activity was greater in female than in male rats, was greater in adult than in prepubertal female rats, increased after castration of male rats, but was not affected by treatment with testosterone propionate or oestradiol benzoate. These regulatory characteristics are in part different from those previously described for the hepatic microsomal 5α reductase. The renal nuclear metabolism of androstenedione, i.e. 5α reduction and 17β hydroxy steroid reduction, was relatively unaffected by sex, age, castration and treatment with testosterone propionate. However, treatment of castrated male rats with oestradiol benzoate led to a significant increase in the 5α reductase activity and a significant decrease in the 17β hydroxy steroid reductase activity. Finally, the nuclear 5α reductase activity in prostate was androgen dependent, decreasing after castration and increasing after treatment with testosterone propionate. In conclusion, the nuclear 5α reductase activities in liver, kidney and prostate seem to be under the control of distinctly different regulatory mechanisms. The hypothesis is presented that whereas the prostatic nuclear 5α reductase participates in the formation of a physiologically active androgen, 5α dihydrotestosterone, this may not be the true function of the nuclear 5α reductase in liver and kidney. These enzymes might rather serve to protect the androgen target sites in the chromatin from active androgens (e.g. testosterone) by transforming them into less active androgens (e.g. 5α androstane 3,17 dione and/or 5α dihydrotestosterone).

Original languageEnglish (US)
Pages (from-to)273-277
Number of pages5
JournalBiochemical Journal
Volume142
Issue number2
DOIs
StatePublished - 1974

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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