Depot-specific steroidogenic gene transcription in human adipose tissue.
BACKGROUND
Sex steroids (androgens and oestrogens) and corticosteroids (glucocorticoids and mineralocorticoids) have a major impact on fat distribution. Several genes involved in steroid synthesis and metabolism, such as 11beta-hydroxysteroid dehydrogenase type 1 and aromatase, are known to be expressed within adipose tissue, thus modulating local steroid levels; however, our knowledge of which genes are expressed and at what level is incomplete.


OBJECTIVE
To detect by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) which of 13 key steroidogenic genes are transcribed within human adipose tissue and to assess whether mRNA levels differ significantly between the subcutaneous abdominal and omental adipose depots.


METHODS
Eight women undergoing caesarean section [age 29.1 +/- 6.5 years, body mass index (BMI) 28.9 +/- 8.4 kg/m(2)].


RESULTS
Genes transcribed in both depots were StAR (steroidogenic acute regulatory protein), CYP11A1 (side-chain cleavage enzyme), HSD3B2 (3beta-hydroxysteroid dehydrogenase type 2), CYP21B (21-hydroxylase), CYP19 (aromatase), HSD11B1 (11beta-hydroxysteroid dehydrogenase type 1), HSD17B3, HSD17B5, HSD17B7 (17beta-hydroxysteroid dehydrogenase types 3, 5 and 7) and SRD5A2 (5alpha-reductase type 2). All but SRD5A2 varied significantly in abundance between depots. CYP17 (17alpha-hydroxylase), CYP11B1 (11beta-hydroxylase) and CYP11B2 (aldosterone synthase) transcription were not detected.


CONCLUSIONS
This study confirms and significantly extends our knowledge of steroidogenic gene expression within adipose tissue, showing that transcript levels are depot specific. We have demonstrated that de novo synthesis from cholesterol of sex steroids, cortisol and aldosterone is not possible because of the absence of key steroidogenic mRNAs. Instead, the pattern of transcription suggests that 11-deoxycorticosterone, a mineralocorticoid, would be the ultimate product of any de novo adipose synthesis.
MacKenzie
Scott M
SM
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom. smmk1w@clinmed.gla.ac.uk
Huda
Shahzya S
SS
Sattar
Naveed
N
Fraser
Robert
R
Connell
John M C
JM
Davies
Eleanor
E
D000273:Adipose Tissue / Q000201:enzymology*; D000311:Adrenal Glands / Q000378:metabolism; D000328:Adult; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D003900:Desoxycorticosterone / Q000096:biosynthesis; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D009852:Omentum / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013256:Steroids / Q000096:biosynthesis*; D014158:Transcription, Genetic
D012333:RNA, Messenger; D013256:Steroids; D003900:Desoxycorticosterone; D003577:Cytochrome P-450 Enzyme System