Structure and tissue-specific expression of a novel member of the rat 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) family. The exclusive 3 beta-HSD gene expression in the skin.
Structures of cDNA clones encoding three members of the rat 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) family were characterized. To search for potential new types of 3 beta-HSD, rat types I and II 3 beta-HSD cDNAs were used as probes to screen a rat genomic DNA library. Among the clones isolated, one encodes a novel predicted rat 3 beta-HSD isoenzyme, chronologically designated type IV. The corresponding full-length cDNA was thereafter isolated by selective polymerase chain reaction amplification from rat ovary and day-15 placenta cDNA libraries. The rat type IV 3 beta-HSD cDNA encodes a predicted 372-amino acid protein of 41,854 daltons, which shares 90.9, 87.9, and 78.8% sequence identity with rat types I, II, and III proteins, respectively. Ribonuclease protection assay reveals that type IV 3 beta-HSD is the sole 3 beta-HSD mRNA species detectable in the skin and represents the predominant species in the placenta while being also detectable in the ovary and, to a lower degree, in the adrenal gland. Transient expression of type IV cDNA in SW-13 cells indicates 3 beta-HSD activity similar to that of rat type I 3 beta-HSD. The presence of multiple 3 beta-HSD genes should permit differential and tissue-specific regulation of this rate-limiting enzymatic activity essential in the biosynthesis of all classes of steroid hormones in both classical steroidogenic and intracrine peripheral tissues.
Simard
J
J
Medical Research Council Group in Molecular Endocrinology, CHUL Research Center, Québec, Canada.
Couet
J
J
Durocher
F
F
Labrie
Y
Y
Sanchez
R
R
Breton
N
N
Turgeon
C
C
Labrie
F
F
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009097:Multienzyme Complexes / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D009838:Oligodeoxyribonucleotides; D009928:Organ Specificity; D011061:Poly A / Q000235:genetics / Q000302:isolation & purification; D011375:Progesterone Reductase / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000201:enzymology*; D013045:Species Specificity; D013251:Steroid Isomerases / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism
C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; D007527:Isoenzymes; D009097:Multienzyme Complexes; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D011061:Poly A; D012313:RNA; D004247:DNA; D011375:Progesterone Reductase; D013251:Steroid Isomerases