Tissue-specific transcription profiles of sex steroid biosynthesis enzymes and the androgen receptor.
17beta-hydroxysteroid dehydrogenase (17beta-HSD) and 5alpha-reductase isoenzymes play a crucial role in the formation and metabolism of sex steroids. Not only the key androgens testosterone and dihydrotestosterone but also their precursors are potent activators of the androgen receptor and are, therefore, likely to act as determinants of male sexual differentiation and maturation in a differentially regulated way. The aim of the present study was to relatively quantify the expression of the mRNA of 17beta-HSD isoenzymes, namely, type 1, 2, 3, 4, 5, 7, and 10, together with the 5alpha-reductase type 1 and 2, and the androgen receptor in normal human males and females. RNA was isolated from peripheral blood cells of both sexes and from genital skin fibroblasts (GSFs) of two different localizations (foreskin and scrotal skin) obtained from phenotypically normal males. mRNA expression was semi-quantified by quantitative reverse-transcriptase polymerase chain reaction with the LightCycler Instrument (Roche). The examined enzymes show statistically significant differences in their transcription pattern between the blood and the GSF RNA samples. Within the GSF samples, there are also significant variations between the two examined localizations in the transcription of 17beta-HSD type 1, 2, 4, and 5 as well as for the androgen receptor. We found large interindividual variation of enzyme transcription patterns in all investigated tissues. In peripheral blood cells, no sex-specific differences were seen. We conclude that sex steroid enzymes are expressed not only in genital primary target tissues but also in peripheral blood. The expression in different target tissues may contribute to both the individual sexual and tissue-specific phenotype in humans.
Department of Pediatrics and Adolescent Medicine, University of Lübeck, Lübeck, Germany.
U
U
Hoppe
P-M
PM
Holterhus
L
L
Wünsch
D
D
Jocham
T
T
Drechsler
S
S
Thiele
C
C
Marschke
O
O
Hiort
D015067:17-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis* / Q000097:blood; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000096:biosynthesis* / Q000097:blood; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002460:Cell Line; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D052816:Foreskin / Q000166:cytology / Q000378:metabolism; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis*; D006801:Humans; D007223:Infant; D007527:Isoenzymes / Q000096:biosynthesis / Q000097:blood; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis; D011944:Receptors, Androgen / Q000096:biosynthesis* / Q000097:blood; D012737:Sex Factors
D012739:Gonadal Steroid Hormones; D007527:Isoenzymes; D012333:RNA, Messenger; D011944:Receptors, Androgen; D015067:17-Hydroxysteroid Dehydrogenases; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase