Depot-specific steroidogenic gene transcription in human adipose tissue.by: Scott M M Mackenzie, Shahzya S S Huda, Naveed Sattar, Robert Fraser, John M C M Connell, Eleanor Davies
Clinical endocrinology (10 April 2008)
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AbstractContext: Sex steroids (androgens and estrogens) 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 realtime 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. Patients: 8 women undergoing caesarean section (age 29.1+/-6.5 years, BMI 28.9+/-8.4kg/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 demonstrate that de novo synthesis from cholesterol of sex steroids, cortisol and aldosterone is not possible due to 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.
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