Depot-specific steroidogenic gene transcription in human adipose tissue

Huda, S. S., MacKenzie, S. M., Sattar, N., Fraser, R., Connell, J. M. C. and Davies, E. (2008) Depot-specific steroidogenic gene transcription in human adipose tissue. Clinical Endocrinology, 69(6), pp. 848-854. (doi:10.1111/j.1365-2265.2008.03262.x)

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Publisher's URL: http://dx.doi.org/10.1111/j.1365-2265.2008.03262.x

Abstract

<b>Context</b> 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 11β-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.<p></p> <b>Objective</b> 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.<p></p> <b>Patients</b> Eight women undergoing caesarean section [age 29•1 ± 6•5 years, body mass index (BMI) 28•9 ± 8•4 kg/m<sup>2</sup>].<p></p> <b>Results</b> Genes transcribed in both depots were StAR (steroidogenic acute regulatory protein), CYP11A1 (side-chain cleavage enzyme), HSD3B2 (3β-hydroxysteroid dehydrogenase type 2), CYP21B (21-hydroxylase), CYP19 (aromatase), HSD11B1 (11β-hydroxysteroid dehydrogenase type 1), HSD17B3, HSD17B5, HSD17B7 (17β-hydroxysteroid dehydrogenase types 3, 5 and 7) and SRD5A2 (5α-reductase type 2). All but SRD5A2 varied significantly in abundance between depots. CYP17 (17α-hydroxylase), CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) transcription were not detected.<p></p> <b>Conclusions</b> 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.<p></p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Davies, Professor Eleanor and Connell, Professor John and MacKenzie, Dr Scott and Sattar, Professor Naveed and Fraser, Prof Robert and Huda, Dr Shahzya
Authors: Huda, S. S., MacKenzie, S. M., Sattar, N., Fraser, R., Connell, J. M. C., and Davies, E.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Clinical Endocrinology
Publisher:Wiley-Blackwell Publishing
ISSN:0300-0664
ISSN (Online):1365-2265
Published Online:10 April 2008
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
392521Regulation of aldosterone and cortisol synthesis in hypertension and cardiovascular diseaseEleanor DaviesMedical Research Council (MRC)G0400874Institute of Cardiovascular and Medical Sciences
392522Regulation of aldosterone and cortisol synthesis in hypertension and cardiovascular diseaseEleanor DaviesMedical Research Council (MRC)G0400874Institute of Cardiovascular and Medical Sciences