Structural and biochemical properties of cloned and expressed human and rat steroid 5. alpha. -reductases

Journal Article · Tue May 01 00:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.87.10.3640· OSTI ID:5451557

Andersson, S; Russell, D W ^[1]

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1. Univ. of Texas Southwestern Medical Center, Dallas (USA)

The microsomal enzyme steroid 5{alpha}-reductase is responsible for the conversion of testosterone into the more potent androgen dihydrotestosterone. In man, this steroid acts on a variety of androgen-responsive target tissues to mediate such diverse endocrine processes as male sexual differentiation in the fetus and prostatic growth in men. Here we describe the isolation, structure, and expression of a cDNA encoding the human steroid 5{alpha}-reductase. A rat cDNA was used as a hybridization probe to screen a human prostate cDNA library. A 2.1-kilobase cDNA was identified and DNA sequence analysis indicated that the human steroid 5{alpha}-reductase was a hydrophobic protein of 259 amino acids with a predicted molecular weight of 29,462. A comparison of the human and rat protein sequences revealed a 60% identity. Transfection of expression vectors containing the human and rat cDNAs into simian COS cells resulted in the synthesis of high levels of steroid 5{alpha}-reductase enzyme activity. Both enzymes expressed in COS cells showed similar substrate specificities for naturally occurring steroid hormones. However, synthetic 4-azasteroids demonstrated marked differences in their abilities to inhibit the human and rat steroid 5{alpha}-reductases.

• OSTI ID: 5451557
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 87:10; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ANDROGENS
METABOLISM
OXIDOREDUCTASES
AMINO ACID SEQUENCE
RECOMBINANT DNA
DNA SEQUENCING
AMPHIBIANS
BIOCHEMISTRY
CARBON 14 COMPOUNDS
DNA HYBRIDIZATION
DNA-CLONING
MAN
OOCYTES
PHOSPHORUS 32
RATS
ANDROSTANES
ANIMALS
AQUATIC ORGANISMS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARBON COMPOUNDS
CHEMISTRY
CLONING
DAYS LIVING RADIOISOTOPES
DNA
ENZYMES
GERM CELLS
HORMONES
HYBRIDIZATION
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
MAMMALS
MOLECULAR STRUCTURE
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PHOSPHORUS ISOTOPES
PRIMATES
RADIOISOTOPES
RODENTS
STEROID HORMONES
STEROIDS
STRUCTURAL CHEMICAL ANALYSIS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques