Isoenzyme type 1 of 5alpha-reductase is abundantly transcribed in normal human genital skin fibroblasts and may play an important role in masculinization of 5alpha-reductase type 2 deficient males.
OBJECTIVE
5alpha-reductase enzymes reduce testosterone (T) to the most potent androgen dihydrotestosterone (DHT). Two isoenzymes are known to day. While the type 2-enzyme (5RII) is predominantly expressed in male genital tissues and mutations are known to cause a severe virilization disorder in genetic males, the role of the type 1-enzyme (5RI) in normal male androgen physiology is unclear. We investigated whether 5RI is transcribed in normal male genital skin fibroblasts (GSFs) and if the transcription is regulated by age or by androgens themselves.


METHODS
GSF from 14 normally virilized males of different ages, ranging from 8 months to 72 years, obtained at circumcision were cultured. Total RNA was isolated after incubation for 48 h with 100 nM T or without androgens. Each sample was amplified in triplicate by real-time PCR with porphobilinogen desaminase as a housekeeping gene used for semiquantification. Selected cultures were analyzed after incubation with 10 and 100 nM T and 1 and 100 nM DHT for 24, 48 and 120 h.


RESULTS
5RI was transcribed in all investigated samples with a 4.5-fold variability in the mRNA concentration of different individuals. However, neither age-related regulation nor significant influence of T or DHT on the transcription rate was discovered.


CONCLUSIONS
Since 5RI is abundantly transcribed in GSFs, we hypothesize that this isoenzyme may play important roles in the androgen physiology of normally virilized males and may contribute to masculinization in 5RII-deficient males at the time of puberty.
Thiele
Susanne
S
Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University of Lübeck, Lübeck, Germany.
Hoppe
Ute
U
Holterhus
Paul-Martin
PM
Hiort
Olaf
O
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D000328:Adult; D000367:Age Factors; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005347:Fibroblasts; D005837:Genitalia, Male / Q000201:enzymology*; D006801:Humans; D007223:Infant; D007527:Isoenzymes; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012733:Sex Differentiation / Q000502:physiology; D013739:Testosterone / Q000378:metabolism; D014158:Transcription, Genetic
D007527:Isoenzymes; D013739:Testosterone; D012313:RNA; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C476566:steroid-5alpha-reductase type 1